Therapeutic methods and compositions for treating movement disorders

Abstract

The invention provides therapeutic methods, pharmaceutical compositions, and unit dose formulations for treating movement disorders, such as using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator to treat the movement disorder, such as dystonia. In some aspects, the invention provides a method of treating a movement disorder in a patient, where the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

Description

THERAPEUTIC METHODS AND COMPOSITIONS FOR TREATING MOVEMENT DISORDERS CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the priority benefit of U. S. Provisional Application No.63 / 813,518, filed May 28, 2025, and U. S. Provisional Application No. 63 / 715,318, filed November 1, 2024, which are each hereby incorporated by reference in their entirety.FIELD OF THE INVENTION10002] The invention provides therapeutic methods, pharmaceutical compositions, and unit dose formulations for treating movement disorders, such as using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator to treat dystonia.BACKGROUND

[0003] Movement disorders impact a substantial number of patients. One such movement disorder, dystonia, is a neurological movement disorder characterized by involuntary (unintended) muscle contractions that cause slow repetitive movements or abnormal postures that can sometimes be painful. The condition can affect one part of the body (focal dystonia), two or more adjacent parts (segmental dystonia), or multiple parts of the body (general dystonia) including the trunk. The muscle spasms can range from mild to severe. Dystonia can be described as primary or secondary. Primary dystonia is when the dystonia is the sole neurological condition experienced by a subject. Secondary dystonia is when the dystonia is caused by outside factors and can be attributed to a specific cause such as exposure to certain medications, toxins, infections, stroke, spinal cord injury, head injury, or peripheral injury. Dystonia is reported to be associated with over activity of cholinergic interneurons (Chis) that provide acetylcholine (Ach) to medium spiny neurons (MSNs). Overactivity of cholinergic interneurons produces more acetylcholine for signaling to medium spiny neurons and other neuronal populations leading to dystonia. Treatment options currently available for patients with dystonia do not provide adequate therapeutic benefit for all patients and / or have significant adverse side effects.

[0004] Trihexyphenidyl-HCl (THP), a phenyl propylamine, is an anticholinergic agent that was first approved by the FDA in 1949. THP is a synthetic antispasmodic drug that is widely used in the treatment of patients with parkinsonism, including primary or idiopathicParkinson’s disease, secondary symptomatic parkinsonism (postencephalitic, arteriosclerotic, infection-induced, tumor-induced, trauma-induced, and drug-induced), and involuntary movements due to side effects of certain psychiatric drugs. See, for example, Cheung et al. in “Pharmacokinetic evaluation of a sustained release formulation of trihexyphenidyl in healthy volunteers” J. Pharm. Sci. (1988) 77(9):748-50. THP is approved by the FDA as an adjunct in the treatment of parkinsonism and for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones. THP is widely used off-label for treating certain types of dystonia.However, there are major problems associated with using THP to treat dystonia and Parkinsonism, including that it causes significant adverse side effects at the dosage typically used to treat dystonia and current reports describe frequent administration of THP; each of the foregoing contribute to poor patient compliance with THP therapy and concomitant poor therapeutic outcomes.

[0005] Accordingly, the need exists for new therapeutic methods and pharmaceutical compositions for treating movement disorders, including dystonia. The present invention addresses the foregoing needs and provides other related advantages.SUMMARY

[0006] The invention provides therapeutic methods, pharmaceutical compositions, and unit dose formulations for treating movement disorders, such as using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator to treat dystonia. In particular, one aspect of the invention provides a method of treating a movement disorder in a patient, where the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder. The muscarinic acetylcholine receptor inhibitor may be, for example, trihexyphenidyl or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor activator may be, for example, bethanechol or a pharmaceutically acceptable salt thereof. Use of the muscarinic acetylcholine receptor inhibitor in combination with the muscarinic acetylcholine receptor activator reduces the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, and also provides the further benefit of permitting a higherdose of muscarinic acetylcholine receptor inhibitor to be administered to the patient while maintaining a side effect profile that is tolerable for patients. Use of the muscarinic acetylcholine receptor inhibitor in combination with the muscarinic acetylcholine receptor activator also allows for a subject taking the combination to initiate treatment at a dose of the muscarinic receptor inhibitor that is higher than taking the muscarinic receptor inhibitor alone. Such combination also allows for fewer doses of the muscarinic receptor inhibitor at a subtherapeutic dose before reaching a therapeutic dose compared to administering the muscarinic receptor inhibitor alone.

[0007] Certain aspects of the present disclosure provide a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator, wherein the muscarinic acetylcholine receptor activator does not prevent the therapeutic benefit of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder. In some aspects, muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered simultaneously to the patient.

[0008] In some aspects, the method comprises administering to a patient in need thereof (i) a therapeutically effective amount of a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess or a pharmaceutically acceptable salt thereof and (ii) a muscarinic acetylcholine receptor activator, to thereby treat the movement disorder. Use of the muscarinic acetylcholine receptor inhibitor in combination with the muscarinic acetylcholine receptor activator reduces the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, and also provides the further benefit of permitting a higher dose of muscarinic acetylcholine receptor inhibitor to be administered to the patient while maintaining a side effect profile that is tolerable for patients. In some aspects, the muscarinic acetylcholine receptor inhibitor is (R)-THP.

[0009] In some aspects, provided is an oral pharmaceutical composition comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, and (iii) a pharmaceutically acceptable carrier. The muscarinic acetylcholine receptor inhibitor may be, for example, trihexyphenidyl or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor inhibitormay be, for example, trihexyphenidyl hydrochloride. The muscarinic acetylcholine receptor activator may be, for example, bethanechol or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor activator may be, for example, bethanechol chloride.

[0010] In some aspects, provided is a pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess or a pharmaceutically acceptable salt thereof, (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier. In some aspects the muscarinic acetylcholine receptor activator is BTC or a pharmaceutically acceptable salt thereof. In some aspects, the pharmaceutical composition comprises (i) (R)-THP having a stereochemical purity of at least 95% enantiomeric excess (ii) BTC, and (iii) a pharmaceutically acceptable carrier.

[0011] In some aspects, provided is a pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess or a pharmaceutically acceptable salt thereof, (ii) a muscarinic acetylcholine receptor activator selected from racemic bethanechol or a pharmaceutically acceptable salt thereof, and (iii) a pharmaceutically acceptable carrier.

[0012] In some aspects, provided is a pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess or a pharmaceutically acceptable salt thereof, (ii) a muscarinic acetylcholine receptor activator selected from (S)-bethanechol having a stereochemical purity of at least 95% enantiomeric excess or a pharmaceutically acceptable salt thereof, and (iii) a pharmaceutically acceptable carrier. The pharmaceutical composition may be, for example, formulated for oral administration.

[0013] In some aspects, provided is a pharmaceutical composition described herein for use in medicine. In some aspects, provided is a pharmaceutical composition described herein for use in the treatment of a disorder described herein, such as movement disorders described herein. The muscarinic acetylcholine receptor inhibitor may be, for example, trihexyphenidyl or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor inhibitor may be, for example, trihexyphenidyl hydrochloride. The muscarinic acetylcholine receptor activator may be, for example, bethanechol or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor activator may be, for example, bethanechol chloride. Insome aspects, the trihexyphenidyl or a pharmaceutically acceptable salt thereof is racemic trihexyphenidyl. In some aspects, the trihexyphenidyl or a pharmaceutically acceptable salt thereof is (R)-trihexyphenidyl. In some aspects, the (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess. In some aspect, the bethanechol or a pharmaceutically acceptable salt thereof is racemic bethanechol. In some aspects, the bethanechol or a pharmaceutically acceptable salt thereof is (S)-bethanechol. In some aspects, the (S)-bethanechol or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof that has a stereochemical purity of at least 95% enantiomeric excess, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0014] In some aspects, the movement disorder is dystonia. In some aspects, the movement disorder is primary dystonia. In some aspects, the movement disorder is secondary dystonia. In some aspects, the movement disorder is tardive dystonia. In some aspects, the movement disorder is drug-induced dystonia. In some aspects, the movement disorder is cerebral palsy-associated dystonia. In some aspects, the movement disorder is segmental dystonia. In some aspects, the movement disorder is hemidystonia. In some aspects, the movement disorder is multifocal dystonia. In some aspects, the movement disorder is generalized dystonia. In some aspects, the movement disorder is idiopathic in origin. In some aspects, the movement disorder is a genetic dystonia. In some aspects, the genetic dystonia is associated with a mutation in one or more genes selected from TORI A, THAP1, ANO3, GNAL, KMT2B, GCH1, SPR, TAF1, PRKRA, ATP1A3, SGCE, PNKD, PRRT2, SLC2A1, and ECHS1.

[0015] In some aspects, the movement disorder is focal dystonia. In some aspects, the focal dystonia is cervical dystonia. In some aspects, the focal dystonia is blepharospasm. In some aspects, the focal dystonia is hand dystonia. In some aspects, the focal dystonia is writer’s cramp. In some aspects, the focal dystonia is musician’s dystonia. In some aspects, the focal dystonia is leg dystonia. In some aspects, the focal dystonia is foot dystonia. In some aspects, the movement disorder is Multiple System Atrophy, Progressive Supranuclear Palsy, or tremor.

[0016] In some aspects, the movement disorder is Parkinson’s disease. In some aspects, the movement disorder is tremor in Parkinson’s disease. In some aspects, the movement disorder is drug-induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies.

[0017] In some aspects, provided is a combination comprising a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator. In some aspects, the combination is for use medicine. In some aspects, the combination is for use in the treatment of a disorder described herein, such as movement disorders described herein. The muscarinic acetylcholine receptor inhibitor may be, for example, trihexyphenidyl or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor inhibitor may be, for example, trihexyphenidyl hydrochloride. The muscarinic acetylcholine receptor activator may be, for example, bethanechol or a pharmaceutically acceptable salt thereof. The muscarinic acetylcholine receptor activator may be, for example, bethanechol chloride. In some aspects, the trihexyphenidyl or a pharmaceutically acceptable salt thereof is racemic trihexyphenidyl. In some aspects, the trihexyphenidyl or a pharmaceutically acceptable salt thereof is (R)-trihexyphenidyl. In some aspects, the (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess. In some aspect, the bethanechol or a pharmaceutically acceptable salt thereof is racemic bethanechol. In some aspects, the bethanechol or a pharmaceutically acceptable salt thereof is (S)-bethanechol. In some aspects, the (S)-bethanechol or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess, and the muscarinic acetylcholine receptor activator is (S)-bethanechol or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess.

[0018] In some aspects, the muscarinic acetylcholine receptor inhibitor is administered to a patient in a fasted state. In some aspects, the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state. In some aspects, the muscarinic acetylcholine receptor inhibitor is administered to a patient in a fed state. In some aspects, the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fed state. In some aspects, the muscarinic acetylcholine receptor inhibitor is provided in a sustained release dosage form. In some aspects, the muscarinic acetylcholine receptor activator is provided in a sustained release dosage form. In some aspects, the muscarinic acetylcholinereceptor activator is provided in an immediate release dosage form. In some aspects, the the pharmaceutical composition comprises (i) a controlled release component containing the muscarinic acetylcholine receptor inhibitor and (ii) an immediate release component containing the muscarinic acetylcholine receptor activator.

[0019] In some aspects, the the pharmaceutical composition is administered orally to the patient. In some aspects, pharmaceutical composition is administered daily. In some aspects, the pharmaceutical composition is administered twice per day. In some aspects, pharmaceutical composition is administered three times per day.

[0020] In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage that, in the absence of a muscarinic acetylcholine receptor activator, causes at least one adverse side effect selected from dry mouth, dry eye, blurry vision, tachycardia, confusion, forgetfulness, hallucination, constipation, urine retention, and brain fog.

[0021] In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at an initial dosage of greater than 1 mg / day. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at an initial dosage of greater than 2 mg / day. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at an initial dosage of greater than 2.5 mg / day. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at an initial dosage of greater than 5 mg / day. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at an initial dosage of greater than 10 mg / day.

[0022] In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage in the range of from about 1 mg to about 10 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage in the range of from about 10 mg to about 20 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 2.5 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 5 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 10 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 15 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage in the range of from about 12.5 mg to about 22.5 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage in the range of from about 20 mg to about 30 mg. In some aspects,the muscarinic acetylcholine receptor activator is orally administered at a dosage in the range of from about 40 mg to about 60 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage in the range of from about 60 mg to about 120 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 90 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 25 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 50 mg. In some aspects, the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 75 mg. In some aspects, the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70 to about 80 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 2.5 mg, and the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 12.5 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 5 mg, and the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 25 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 10 mg, and the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 50 mg. In some aspects, the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 15 mg, and the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 75 mg.

[0023] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 10-20 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70-80 mg.

[0024] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and wherein the (R)-THP is orally administered at a dosage of about 2.5 mg.

[0025] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 2.5 mg, and wherein the BTC is orally administered at a dosage of about 12.5 mg.

[0026] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 5 mg, and wherein the BTC is orally administered at a dosage of about 25 mg.

[0027] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 10 mg, and wherein the BTC is orally administered at a dosage of about 50 mg.

[0028] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptorinhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 15 mg, and wherein the BTC is orally administered at a dosage of about 75 mg.

[0029] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, wherein the (R)-THP is orally administered at a dosage of about 2.5 mg, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state.

[0030] In some aspects, muscarinic acetylcholine receptor inhibitor distributes to the central nervous system and the peripheral nervous system in the patient. In some aspects, muscarinic acetylcholine receptor activator distributes predominately to the peripheral nervous system in the patient.

[0031] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 2.5 mg, and wherein the BTC is orally administered at a dosage of about 12.5 mg, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state.

[0032] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the(R)-THP is orally administered at a dosage of about 5 mg, and wherein the BTC is orally administered at a dosage of about 25 mg, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state.

[0033] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 10 mg, and wherein the BTC is orally administered at a dosage of about 50 mg, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state.

[0034] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 15 mg, and wherein the BTC is orally administered at a dosage of about 75 mg, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state.

[0035] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, wherein the (R)-THP is orally administered at a dosage of about 2.5 mg, and wherein the (R)-THP is provided in a sustained released dosage form.

[0036] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 2.5 mg, wherein the BTC is orally administered at a dosage of about 12.5 mg, and wherein the (R)-THP and BTC are provided in a sustained released dosage form.

[0037] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 5 mg, wherein the BTC is orally administered at a dosage of about 25 mg, and wherein the (R)-THP and BTC are provided in a sustained released dosage form.

[0038] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 10 mg, wherein the BTC is orally administered at a dosage of about 50 mg, and wherein the (R)-THP and BTC are provided in a sustained released dosage form.

[0039] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii)a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 15 mg, wherein the BTC is orally administered at a dosage of about 75 mg, and wherein the R)-THP and BTC are provided in a sustained released dosage form.

[0040] In some aspects, the present disclosure provides a method of treating dystonia in a patient, comprising administering to a patient in need thereof a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the dystonia, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and wherein the (R)-THP is orally administered at a dosage of about 2.5 mg.

[0041] In some aspects, the present disclosure provides a method of treating dystonia in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the dystonia and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the dystonia, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the R)-THP is orally administered at a dosage of about 2.5 mg, and wherein the BTC is orally administered at a dosage of about 12.5 mg.

[0042] In some aspects, the present disclosure provides a method of treating dystonia in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the dystonia and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the dystonia, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the R)-THP is orally administered at a dosage of about 5 mg, and wherein the BTC is orally administered at a dosage of about 25 mg.

[0043] In some aspects, the present disclosure provides a method of treating dystonia in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholinereceptor inhibitor in an amount effective to treat the dystonia and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the dystonia, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 10 mg, and wherein the BTC is orally administered at a dosage of about 50 mg.

[0044] In some aspects, the present disclosure provides a method of treating dystonia in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the dystonia and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the dystonia, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 15 mg, and wherein the BTC is orally administered at a dosage of about 75 mg.

[0045] In some aspects, the present disclosure provides a method of treating Parkinson's Disease in a patient, comprising administering to a patient in need thereof a muscarinic acetylcholine receptor inhibitor in an amount effective to treat Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and wherein the (R)-THP is orally administered at a dosage of about 2.5 mg.

[0046] In some aspects, the present disclosure provides a method of treating Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 2.5 mg, and wherein the BTC is orally administered at a dosage of about 12.5 mg.

[0047] In some aspects, the present disclosure provides a method of treating Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinicacetylcholine receptor inhibitor in an amount effective to treat Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (?)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 5 mg, and wherein the BTC is orally administered at a dosage of about 25 mg.

[0048] In some aspects, the present disclosure provides a method of treating Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 10 mg, and wherein the BTC is orally administered at a dosage of about 50 mg.

[0049] In some aspects, the present disclosure provides a method of treating Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 15 mg, and wherein the BTC is orally administered at a dosage of about 75 mg.

[0050] In some aspects, the present disclosure provides a method of treating tremor in Parkinson's Disease in a patient, comprising administering to a patient in need thereof a muscarinic acetylcholine receptor inhibitor in an amount effective to treat tremor in Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and wherein the (R)-THP is orally administered at a dosage of about 2.5 mg.

[0051] In some aspects, the present disclosure provides a method of treating tremor in Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) amuscarinic acetylcholine receptor inhibitor in an amount effective to treat tremor in Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat tremor in Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (?)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (7 / J-THP is orally administered at a dosage of about 2.5 mg, and wherein the BTC is orally administered at a dosage of about 12.5 mg.

[0052] In some aspects, the present disclosure provides a method of treating tremor in Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat tremor in Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat tremor in Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 5 mg, and wherein the BTC is orally administered at a dosage of about 25 mg.

[0053] In some aspects, the present disclosure provides a method of treating tremor in Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat tremor in Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat tremor in Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 10 mg, and wherein the BTC is orally administered at a dosage of about 50 mg.

[0054] In some aspects, the present disclosure provides a method of treating tremor in Parkinson's Disease in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat tremor in Parkinson's Disease and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of themuscarinic acetylcholine receptor inhibitor, to thereby treat tremor in Parkinson's Disease, wherein the muscarinic acetylcholine receptor inhibitor is (?)-THP, and the muscarinic acetylcholine receptor activator is BTC, wherein the (R)-THP is orally administered at a dosage of about 15 mg, and wherein the BTC is orally administered at a dosage of about 75 mg.

[0055] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is a human patient aged 65 years or older.

[0056] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(minimum) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0057] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(trough) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0058] In some aspects, the present disclosure provides an oral pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat a movement disorder and (ii) a muscarinic acetylcholine receptor activator, and (iii) apharmaceutically acceptable carrier, wherein the composition is sufficient to provide an in vivo plasma profile of the muscarinic acetylcholine receptor inhibitor when administered to a subject in need thereof, wherein the plasma C(minimum) of muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml.

[0059] In some aspects, the present disclosure provides an oral pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat a movement disorder and (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier, wherein the composition is sufficient to provide an in vivo plasma profile of the acetylcholine receptor inhibitor wherein when administered to a patient in need thereof, wherein the plasma C(trough) of muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml.

[0060] In some aspects, the the rate of rise of the plasma concentration of the muscarinic acetylcholine receptor inhibitor is less than about 10 ng / mL / hr.

[0061] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the efficacious dose of muscarinic acetylcholine receptor inhibitor is reached one day after administration. In some aspecs, the the efficacious dose is reached twenty-eight days after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the efficacious dose is reached twenty -two days after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the efficacious dose is reached twenty-one days after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the efficacious dose is reached fourteen days after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the efficacious dose is reached seven days after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the efficacious dose is reached five days after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the efficacious dose is reached one day after administration of the muscarinic acetylcholine receptor inhibitor. In some aspects, the muscarinic acetylcholine receptor inhibitor is (R)-THP or a pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholinereceptor activator is BTC or a pharmaceutically acceptable salt thereof, and wherein the efficacious dose is reached 22 days after administration of the (R)-THP.

[0062] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof, about 10% by weight hydroxpropyl methylcellulose 100SR, about 30% by weight hydroxpropyl methylcellulose 15,000SR, about 10% by weight microcrystalline cellulose, about 44% by weight dicalcium phosphate anhydrous, about 2.2% by weight lactose, and about 1% by weight magnesium stearate.

[0063] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof, about 20 mg hydroxpropyl methylcellulose 100SR, about 60 mg hydroxpropyl methylcellulose 15,000SR, about 20 mg microcrystalline cellulose, about 88 mg dicalcium phosphate anhydrous, about 4.4 mg lactose, and about 2 mg magnesium stearate.

[0064] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof, about 30% by weight hydroxpropyl methylcellulose 100SR, about 10% by weight hydroxpropyl methylcellulose 15,000SR, about 10% by weight microcrystalline cellulose, about 44% by weight dicalcium phosphate anhydrous, about 2.2% by weight lactose, and about 1% by weight magnesium stearate.

[0065] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof, about 60 mg hydroxpropyl methylcellulose 100SR, about 20 mg hydroxpropyl methylcellulose 15,000SR, about 20 mg microcrystalline cellulose, about 88 mg dicalcium phosphate anhydrous, about 4.4 mg lactose, and about 2 mg magnesium stearate.

[0066] In some aspects, the present disclosure provides a composition pharmaceutical comprising about 5.6% by weight R-THP or a pharmaceutically acceptable salt thereof, about 30% by weight hydroxpropyl methylcellulose 100SR, about 10% by weight microcrystalline cellulose, about 53.4% by weight lactose, and about 1% by weight magnesium stearate.

[0067] In some aspects, the present disclosure provides a pharmaceutical comprising about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof, about 30 mg hydroxpropyl methylcellulose 100SR, about 10 mg microcrystalline cellulose, about 53.4 mg lactose, and about 1 mg magnesium stearate.

[0068] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof, about 10% by weight hydroxpropyl methylcellulose 100SR, about 30% by weight hydroxpropyl methylcellulose 15,000SR, about 20% by weight microcrystalline cellulose, about 23.75% by weight dicalcium phosphate anhydrous, and about 1% by weight magnesium stearate.

[0069] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 30.5 mg BTC or a pharmaceutically acceptable salt thereof, about 20 mg hydroxpropyl methylcellulose 100SR, about 60 mg hydroxpropyl methylcellulose 15,000SR, about 40 mg microcrystalline cellulose, about 47.5 mg dicalcium phosphate anhydrous, and about 2 mg magnesium stearate.

[0070] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof, about 5-15% by weight hydroxpropyl methylcellulose 100SR, about 25-35% by weight hydroxpropyl methylcellulose 15,000SR, about 5-15% by weight microcrystalline cellulose, about 40-50% by weight dicalcium phosphate anhydrous, about 1-5% by weight lactose, and about 0.1-3% by weight magnesium stearate.

[0071] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof, about 15-25 mg hydroxpropyl methylcellulose 100SR, about 55-65 mg hydroxpropyl methylcellulose 15,000SR, about 15-25 mg microcrystalline cellulose, about 83-93 mg dicalcium phosphate anhydrous, about 1-10 mg lactose, and about 0.5-5 mg magnesium stearate.

[0072] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof, about 25-35% by weight hydroxpropyl methylcellulose 100SR, about 5-15% by weight hydroxpropyl methylcellulose 15,000SR, about 5-15% by weight microcrystalline cellulose, about 40-50% by weight dicalcium phosphate anhydrous, about 1-5% by weight lactose, and about 0.1-3% by weight magnesium stearate.

[0073] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof, about 55-65 mg hydroxpropyl methylcellulose 100SR, about 15-25 mg hydroxpropyl methylcellulose 15,000SR, about 15-25 mg microcrystalline cellulose, about 83-93 mg dicalcium phosphate anhydrous, about 1-10 mg lactose, and about 0.1-3 mg magnesium stearate.

[0074] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1-10% by weight R-THP or a pharmaceutically acceptable salt thereof, about 25-35% by weight hydroxpropyl methylcellulose 100SR, about 5-15% by weight microcrystalline cellulose, about 47-57% by weight lactose, and about 0.1-3% by weight magnesium stearate.

[0075] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof, about 25-35 mg hydroxpropyl methylcellulose 100SR, about 5-15 mg microcrystalline cellulose, about 47-57 mg lactose, and about 0.1-3 mg magnesium stearate.

[0076] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 1.4 % by weight R-THP or a pharmaceutically acceptable salt thereof, about 10% by weight hydroxpropyl methylcellulose 100SR, about 30% by weight hydroxpropyl methylcellulose 15,000SR, about 10% by weight microcrystalline cellulose, about 44% by weight dicalcium phosphate anhydrous, about 3.6% by weight lactose; and about 1% by weight magnesium stearate.

[0077] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 2.8 mg R-THP or a pharmaceutically acceptable salt thereof, about 20 mg hydroxpropyl methylcellulose 100SR, about 60 mg hydroxpropyl methylcellulose 15,000SR, about 20 mg microcrystalline cellulose, about 88 mg dicalcium phosphate anhydrous, about 7.2 mg lactose, and about 1 mg magnesium stearate.

[0078] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 0.1-3 % by weight R-THP or a pharmaceutically acceptable salt thereof, about 5-15% by weight hydroxpropyl methylcellulose 100SR, about 25-35% by weight hydroxpropyl methylcellulose 15,000SR, about 5-15% by weight microcrystalline cellulose, about 39-49% by weight dicalcium phosphate anhydrous, about 1-8% by weight lactose, and about 0.1-3% by weight magnesium stearate.

[0079] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 0.1-5 mg R-THP or a pharmaceutically acceptable salt thereof, about 15-25 mg hydroxpropyl methylcellulose 100SR, about 55-65 mg hydroxpropyl methylcellulose 15,000SR, about 15-25 mg microcrystalline cellulose, about 83-93 mg dicalcium phosphate anhydrous, about 2-12 mg lactose; and about 0.1-3 mg magnesium stearate.

[0080] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 11.2 mg R-THP or a pharmaceutically acceptable salt thereof, about 20 mg hydroxpropyl methylcellulose 100SR, about 60 mg hydroxpropyl methylcellulose 15,000SR, about 20 mg microcrystalline cellulose, about 86.8 mg dicalcium phosphate anhydrous, and about 2 mg magnesium stearate.

[0081] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 5.6 % by weight R-THP or a pharmaceutically acceptable salt thereof, about 10% by weight hydroxpropyl methylcellulose 100SR, about 30% by weight hydroxpropyl methylcellulose 15,000SR, about 10% by weight microcrystalline cellulose, about 43.4% by weight dicalcium phosphate anhydrous, and about 1% by weight magnesium stearate.

[0082] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 6-16 mg R-THP or a pharmaceutically acceptable salt thereof, about 15-25 mg hydroxpropyl methylcellulose 100SR, about 55-65 mg hydroxpropyl methylcellulose 15,000SR, about 15-25 mg microcrystalline cellulose, about 81-91 mg dicalcium phosphate anhydrous, and about 0.1-5 mg magnesium stearate.

[0083] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 0.1-10 % by weight R-THP or a pharmaceutically acceptable salt thereof, about 5-15% by weight hydroxpropyl methylcellulose 100SR, about 25-35% by weight hydroxpropyl methylcellulose 15,000SR, about 5-15% by weight microcrystalline cellulose, about 38-48% by weight dicalcium phosphate anhydrous, and about 0.1-3% by weight magnesium stearate.

[0084] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof, about 5-15% by weight hydroxpropyl methylcellulose 100SR, about 25-35% by weight hydroxpropyl methylcellulose 15,000SR, about 15-25% by weight microcrystalline cellulose, about 18-28% by weight dicalcium phosphate anhydrous, and about 0.1-3% by weight magnesium stearate.

[0085] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 25-35 mg BTC or a pharmaceutically acceptable salt thereof, about 15-25 mg hydroxpropyl methylcellulose 100SR, about 55-65 mg hydroxpropyl methylcellulose115,000SR, about 35-45 mg microcrystalline cellulose, about 43-53 mg dicalcium phosphate anhydrous, and about 0.1-3 mg magnesium stearate.

[0086] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 30.5 mg BTC or a pharmaceutically acceptable salt thereof, about 20 mg hydroxpropyl methylcellulose 100SR, about 60 mg hydroxpropyl methylcellulose 15,000SR, about 40 mg microcrystalline cellulose, about 47.5 mg dicalcium phosphate anhydrous, and about 2 mg magnesium stearate.

[0087] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof, about 10% by weight hydroxpropyl methylcellulose 100SR, about 30% by weight hydroxpropyl methylcellulose 15,000SR, about 20% by weight microcrystalline cellulose, about 23.75% by weight dicalcium phosphate anhydrous, and about 1% by weight magnesium stearate.

[0088] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 61.5 mg BTC or a pharmaceutically acceptable salt thereof, about 20 mg hydroxpropyl methylcellulose 100SR, about 60 mg hydroxpropyl methylcellulose 15,000SR, about 20 mg microcrystalline cellulose, about 37 mg dicalcium phosphate anhydrous, and about 2 mg magnesium stearate.

[0089] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 30.5% by weight BTC or a pharmaceutically acceptable salt thereof, about 10% by weight hydroxpropyl methylcellulose 100SR, about 30% by weight hydroxpropyl methylcellulose 15,000SR, about 10% by weight microcrystalline cellulose, about 18.5% by weight dicalcium phosphate anhydrous, and about 1% by weight magnesium stearate.

[0090] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 122 mg BTC or a pharmaceutically acceptable salt thereof, about 40 mg hydroxpropyl methylcellulose 100SR, about 120 mg hydroxpropyl methylcellulose 15,000SR, about 40 mg microcrystalline cellulose, about 74 mg dicalcium phosphate anhydrous, and about 4 mg magnesium stearate.

[0091] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 56-66 mg BTC or a pharmaceutically acceptable salt thereof, about 15-25 mg hydroxpropyl methylcellulose 100SR, about 55-65 mg hydroxpropyl methylcellulose 15,000SR, about 15-25 mg microcrystalline cellulose, about 32-42 mg dicalcium phosphate anhydrous, and about 0.1-3 mg magnesium stearate.

[0092] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 25-35% by weight BTC or a pharmaceutically acceptable salt thereof, about 5-15% by weight hydroxpropyl methylcellulose 100SR, about 25-35% by weight hydroxpropyl methylcellulose 15,000SR, about 5-15% by weight microcrystalline cellulose, about 13-23% by weight dicalcium phosphate anhydrous, and about 0.1-3% by weight magnesium stearate.

[0093] In some aspects, the present disclosure provides a pharmaceutical composition comprising about 117-127 mg BTC or a pharmaceutically acceptable salt thereof, about 35-45 mg hydroxpropyl methylcellulose 100SR, about 115-125 mg hydroxpropyl methylcellulose 15,000SR, about 35-45 mg microcrystalline cellulose, about 69-79 mg dicalcium phosphate anhydrous, and about 1-8 mg magnesium stearate.

[0094] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof; (b) about 20 mg hydroxpropyl methylcellulose 100SR; (c) about 60 mg hydroxpropyl methylcellulose 15,000SR; (d) about 20 mg microcrystalline cellulose; (e) about 88 mg dicalcium phosphate anhydrous; (f) about 4.4 mg lactose; (g) about 2 mg magnesium stearate; and wherein the sustained release BTC component comprises: (a) about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; (b) about 20 mg hydroxpropyl methylcellulose 100SR; (c) about 60 mg hydroxpropyl methylcellulose 15,000SR; (d) about 40 mg microcrystalline cellulose; (e) about 47.5 mg dicalcium phosphate anhydrous; and (f) about 2 mg magnesium stearate.

[0095] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof; (b) about 60 mg hydroxpropyl methylcellulose 100SR; (c) about 20 mg hydroxpropyl methylcellulose 15,000SR; (d) about 20 mg microcrystalline cellulose; (e) about 88 mg dicalcium phosphate anhydrous; (f) about 4.4 mg lactose; and (g) about 2 mg magnesium stearate; wherein the sustained release BTC component comprises: (a) about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; (b) about 20 mg hydroxpropyl methylcellulose 100SR; (c)about 60 mg hydroxpropyl methylcellulose 15,000SR; (d) about 40 mg microcrystalline cellulose; (e) about 47.5 mg dicalcium phosphate anhydrous; and (f) about 2 mg magnesium stearate.

[0096] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof; (b) about 20 mg hydroxpropyl methylcellulose 100SR; (c) about 60 mg hydroxpropyl methylcellulose 15,000SR; (d) about 20 mg microcrystalline cellulose; (e) about 88 mg dicalcium phosphate anhydrous; (f) about 4.4 mg lactose; and (g) about 2 mg magnesium stearate; wherein the sustained release BTC component comprises: (a) about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; (b) about 20 mg hydroxpropyl methylcellulose 100SR; (c) about 60 mg hydroxpropyl methylcellulose 15,000SR; (d) about 40 mg microcrystalline cellulose; (e) about 47.5 mg dicalcium phosphate anhydrous; and (f) about 2 mg magnesium stearate.

[0097] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: about 2.8 mg R-THP or a pharmaceutically acceptable salt thereof; about 20 mg hydroxpropyl methylcellulose 100SR; about 60 mg hydroxpropyl methylcellulose 15,000SR; about 20 mg microcrystalline cellulose; about 88 mg dicalcium phosphate anhydrous; about 7.2 mg lactose; about 1 mg magnesium stearate; wherein the sustained release BTC component comprises: about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; about 20 mg hydroxpropyl methylcellulose 100SR; about 60 mg hydroxpropyl methylcellulose 15,000SR; about 40 mg microcrystalline cellulose; about 47.5 mg dicalcium phosphate anhydrous; and about 2 mg magnesium stearate.

[0098] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof; (b) about 10% by weight hydroxpropyl methylcellulose 100SR; (c) about 30% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 10% by weight microcrystalline cellulose; (e) about 44% by weight dicalcium phosphate anhydrous; (f) about 2.2% by weight lactose; and (g) about 1% by weight magnesium stearate; wherein the sustained release BTC component comprises: (a) about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; (b) about 10% by weight hydroxpropyl methylcellulose 100SR; (c) about 30% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 20% by weight microcrystalline cellulose; (e) about23.75% by weight dicalcium phosphate anhydrous; and (f) about 1% by weight magnesium stearate.

[0099] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof; (b) about 30% by weight hydroxpropyl methylcellulose 100SR; (c) about 10% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 10% by weight microcrystalline cellulose; (e) about 44% by weight dicalcium phosphate anhydrous; (f) about 2.2% by weight lactose; and (g) about 1% by weight magnesium stearate; wherein the sustained release BTC component comprises: (a) about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; (b) about 10% by weight hydroxpropyl methylcellulose 100SR; (c) about 30% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 20% by weight microcrystalline cellulose; (e) about 23.75% by weight dicalcium phosphate anhydrous; and (f) about 1% by weight magnesium stearate.

[0100] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 5.6% by weight R-THP or a pharmaceutically acceptable salt thereof; (b) about 30% by weight hydroxpropyl methylcellulose 100SR; (c) about 10% by weight microcrystalline cellulose; (d) about 53.4% by weight lactose; and (e) about 1% by weight magnesium stearate; wherein the sustained release BTC component comprises: (a) about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; (b) about 10% by weight hydroxpropyl methylcellulose 100SR; (c) about 30% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 20% by weight microcrystalline cellulose; (e) about 23.75% by weight dicalcium phosphate anhydrous; and (f) about 1% by weight magnesium stearate.

[0101] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof; (b) about 5-15% by weight hydroxpropyl methylcellulose 100SR; (c) about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 5-15% by weight microcrystalline cellulose; (e) about 40-50% by weight dicalcium phosphate anhydrous; (f) about 1-5% by weight lactose; and (g) about 0.1-3% byweight magnesium stearate; wherein the sustained release BTC component comprises: (a) about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof; (b) about 5-15% by weight hydroxpropyl methylcellulose 100SR; (c) about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 15-25% by weight microcrystalline cellulose; (e) about 18-28% by weight dicalcium phosphate anhydrous; and (f) about 0.1-3% by weight magnesium stearate.

[0102] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof; (b) about 25-35% by weight hydroxpropyl methylcellulose 100SR; (c) about 5-15% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 5-15% by weight microcrystalline cellulose; (e) about 40-50% by weight dicalcium phosphate anhydrous; (f) about 1-5% by weight lactose; and (g) about 0.1-3% by weight magnesium stearate; wherein the sustained release BTC component comprises: (a) about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof; (b) about 5-15% by weight hydroxpropyl methylcellulose 100SR; (c) about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 15-25% by weight microcrystalline cellulose; (e) about 18-28% by weight dicalcium phosphate anhydrous; and (f) about 0.1-3% by weight magnesium stearate.

[0103] In some aspects, a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof; (b) about 5-15% by weight hydroxpropyl methylcellulose 100SR; (c) about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 5-15% by weight microcrystalline cellulose; (e) about 40-50% by weight dicalcium phosphate anhydrous; (f) about 1-5% by weight lactose; and (g) about 0.1-3% by weight magnesium stearate; wherein the sustained release BTC component comprises: (a) about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof; (b) about 5-15% by weight hydroxpropyl methylcellulose 100SR; (c) about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; (d) about 15-25% by weight microcrystalline cellulose; (e) about 18-28% by weight dicalcium phosphate anhydrous; and (f) about 0.1-3% by weight magnesium stearate.

[0104] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component,wherein the sustained release R-THP component comprises: (a) about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof; (b) about 25-35 mg hydroxpropyl methylcellulose 100SR; (c) about 5-15 mg microcrystalline cellulose; (d) about 47-57 mg lactose; and (e) about 0.1-3 mg magnesium stearate; wherein the sustained release BTC component comprises: (a) about 25-35 mg BTC or a pharmaceutically acceptable salt thereof; (b) about 15-25 mg hydroxpropyl methylcellulose 100SR; (c) about 55-65 mg hydroxpropyl methylcellulose 15,000SR; (d) about 35-45 mg microcrystalline cellulose; (e) about 43-53 mg dicalcium phosphate anhydrous; and (f) about 0.1-3 mg magnesium stearate.

[0105] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof; (b) about 55-65 mg hydroxpropyl methylcellulose 100SR; (c) about 15-25 mg hydroxpropyl methylcellulose 15,000SR; (d) about 15-25 mg microcrystalline cellulose; (e) about 83-93 mg dicalcium phosphate anhydrous; (f) about 1-10 mg lactose; and (g) about 0.1-3 mg magnesium stearate; wherein the sustained release BTC component comprises: (a) about 25-35 mg BTC or a pharmaceutically acceptable salt thereof; (b) about 15-25 mg hydroxpropyl methylcellulose 100SR; (c) about 55-65 mg hydroxpropyl methylcellulose 15,000SR; (d) about 35-45 mg microcrystalline cellulose; (e) about 43-53 mg dicalcium phosphate anhydrous; and (f) about 0.1-3 mg magnesium stearate.

[0106] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: (a) about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof; (b) about 15-25 mg hydroxpropyl methylcellulose 100SR; (c) about 55-65 mg hydroxpropyl methylcellulose 15,000SR; (d) about 15-25 mg microcrystalline cellulose; (e) about 83-93 mg dicalcium phosphate anhydrous; (f) about 1-10 mg lactose; and (g) about 0.5-5 mg magnesium stearate; wherein the sustained release BTC component comprises: (a) about 25-35 mg BTC or a pharmaceutically acceptable salt thereof; about 15-25 mg hydroxpropyl methylcellulose 100SR; (b) about 55-65 mg hydroxpropyl methylcellulose 15,000SR; (c) about 35-45 mg microcrystalline cellulose; (d) about 43-53 mg dicalcium phosphate anhydrous; and (e) about 0.1-3 mg magnesium stearate.

[0107] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: about 2.8 mg R-THP or apharmaceutically acceptable salt thereof; about 20 mg hydroxpropyl methylcellulose 100SR; about 60 mg hydroxpropyl methylcellulose 15,000SR; about 20 mg microcrystalline cellulose; about 88 mg dicalcium phosphate anhydrous; about 7.2 mg lactose; about 1 mg magnesium stearate; wherein the sustained release BTC component comprises: about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; about 20 mg hydroxpropyl methylcellulose 100SR; about 60 mg hydroxpropyl methylcellulose 15,000SR; about 40 mg microcrystalline cellulose; about 47.5 mg dicalcium phosphate anhydrous; and about 2 mg magnesium stearate.

[0108] In some aspects, the present disclosure provides a pharmaceutical composition comprising a sustained release R-THP component and a sustained release BTC component, wherein the sustained release R-THP component comprises: about 1.4% by weight R-THP or a pharmaceutically acceptable salt thereof; about 10% by weight hydroxpropyl methylcellulose 100SR; about 30% by weight hydroxpropyl methylcellulose 15,000SR; about 10% by weight microcrystalline cellulose; about 44% by weight dicalcium phosphate anhydrous; about 3.6% by weight lactose; and about 1% by weight magnesium stearate; wherein the sustained release BTC component comprises: about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; about 10% by weight hydroxpropyl methylcellulose 100SR; about 30% by weight hydroxpropyl methylcellulose 15,000SR; about 20% by weight microcrystalline cellulose; about 23.75% by weight dicalcium phosphate anhydrous; and about 1% by weight magnesium stearate.

[0109] In some aspects, the pharmaceutical composition provides a R-THP plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

[0110] In some aspects, the pharmaceutical composition provides a C(max) plasma concentration of R-THP: BTC of about 1:1 to about 1:20.

[0111] In some aspects, the pharmaceutical composition provides an area under the curve (AUC) plasma concentration of R-THP: BTC of about 1:1 to about 1:40.

[0112] In some aspects, the pharmaceutical composition provides a R-THP C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

[0113] In some aspects, the pharmaceutical composition provides a R-THP C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

[0114] In some aspects, the pharmaceutical composition provides a R-THP: BTC plasma concentration ratio of about 1:5 from between 0 to about 10 hours after administration of the pharmaceutical composition.

[0115] In some aspects, the pharmaceutical composition provides a R-THP: BTC plasma concentration ratio of at least about 1:1.5 from between 0 to about 10 hours after administration of the pharmaceutical composition.

[0116] In some aspects, the pharmaceutical composition provides a R-THP: BTC plasma concentration ratio of 1: 1.5 to about 1:5 from between 0 to about 10 hours after administration of the pharmaceutical composition.

[0117] In some aspects, the pharmaceutical composition is administered to a patient with a movement disorder selected from dystonia, primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-associated dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer’s cramp, musician’s dystonia, leg dystonia, foot dystonia, idiopathic in origin, a genetic dystonia, Multiple System Atrophy, Progressive Supranuclear Palsy, tremor, Parkinson’s disease, tremor in Parkinson’s disease, drug-induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies. In some aspects, the pharmaceutical composition is administered to a patient with dystonia. In some aspects, the pharmaceutical composition is administered to a patient with tremor in Parkinson’s disease.

[0118] In some aspects, the pharmaceutical composition is a bilayer tablet. In some aspects, the the pharmaceutical composition is a microparticulate.

[0119] In some aspects, the pharmaceutical composition is for use as a medicament. In some aspects, the pharmaceutical composition is for use in the treatment of a movement disorder.

[0120] In some aspects, the pharmaceutical composition comprises the R-THP and the BTC in a weight ratio of R-THP to BTC of about 1:5.

[0121] In some aspects, the pharmaceutical composition provides a plasma C(minimum) concentration of the R-THP of greater than or equal to about 25 ng / ml after administration of the pharmaceutical composition.

[0122] In some aspects, the pharmaceutical composition provides a plasma concentration rate of rise of the R-THP is less than or equal to about 10 ng / ml / hr after administration of the pharmaceutical composition.

[0123] In some aspects, the pharmaceutical composition provides an area under the curve (AUC) plasma concentration of the R-THP is about 800 to about 1200 ng*hr / ml after administration of the pharmaceutical composition.

[0124] In some aspects, the pharmaceutical composition provides after administration of the pharmaceutical composition: plasma C(minimum) concentration of the R-THP of greater than or equal to about 25 ng / ml; a plasma concentration rate of rise of the R-THP is less than or equal to about 10 ng / ml / hr; and an area under the curve (AUC) plasma concentration of the R-THP is about 800 to about 1200 ng*hr / ml.

[0125] In some aspects, the magnitude or severity of at least one side effect of the R-THP or a pharmaceutically acceptable salt thereof is reduced in the patient compared to a patient administered an immediate release formulation of trihexyphenidyl or a pharmaceutically acceptable salt thereof alone. In some aspects, the side effect is selected from the group consisting of dry mouth, dry eye, blurry vision, tachycardia, constipation, urine retention, impaired vision, constipation, nausea, cramping, reduced urinary voiding, flushed skin, fever, reduced sweating, cardiac arrhythmia, dizziness, lightheadedness, headache, drowsiness, confusion, reduced concentration, brain fog, euphoria, elevated mood, hallucinations, agitation, irritability, sensory disturbances, blurry vision, brain fog, and combinations thereof.

[0126] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (A)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0127] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amounteffective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the composition demonstrates an area under the curve (AUC) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0128] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (A)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0129] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (A)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0130] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amounteffective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the muscarinic acetylcholine receptor inhibitor demonstrates a plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (A)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0131] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (A)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0132] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition demonstrates an area under the curve (AUC) plasma ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (A)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0133] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a compositioncomprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(minimum) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0134] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(trough) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml. In some aspects, the muscarinic acetylcholine receptor inhibitor is the (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0135] In some aspects, the present disclosure provides a method of treating a movement disorder in a patient in need thereof, comprising administering R-THP and BTC, wherein the R-THP is provided as a sustained release pharmaceutical composition comprising: about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof; about 10% by weight hydroxpropyl methylcellulose 100SR; about 30% by weight hydroxpropyl methylcellulose 15,000SR; about 10% by weight microcrystalline cellulose; about 44% by weight dicalcium phosphate anhydrous; about 2.2% by weight lactose; and about 1% by weight magnesium stearate; and wherein the BTC is provided as a sustained release pharmaceutical composition comprising: about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; about 10% by weight hydroxpropyl methylcellulose 100SR; about 30% by weight hydroxpropyl methylcellulose 15,000SR; about 20% by weight microcrystalline cellulose;about 23.75% by weight dicalcium phosphate anhydrous; and about 1% by weight magnesium stearate

[0136] In some aspects, the R-THP and the BTC are each present in a single pharmaceutical composition that is administered to the patient. In some aspects, the single pharmaceutical composition is a bilayer tablet. In some aspects, the pharmaceutical composition is in the form of a tablet, troche, liquid, drop, capsule, caplet, gel cap, sublingual formulation, bilayer tablet, microparticulate, or spray. In some aspects, the pharmaceutical composition is in the form of a bilayer tablet. In some aspects, the pharmaceutical composition is in the form of a microparticulate.

[0137] In some aspects, the R-THP and the BTC are administered in a weight ratio of R-THP to BTC of about 1:5.

[0138] In some aspects, the movement disorder is selected from dystonia, primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-associated dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer’s cramp, musician’s dystonia, leg dystonia, foot dystonia, idiopathic in origin, a genetic dystonia, Multiple System Atrophy, Progressive Supranuclear Palsy, tremor, Parkinson’s disease, tremor in Parkinson’s disease, drug-induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies. In some aspects, the movement disorder is dystonia. In some aspects, the movement disorder is tremor in Parkinson’s disease.

[0139] In some aspects, the magnitude or severity of at least one side effect of the R-THP or a pharmaceutically acceptable salt thereof is reduced in the patient compared to a patient administered an immediate release formulation of trihexyphenidyl or a pharmaceutically acceptable salt thereof alone. In some aspects, the side effect is selected from the group consisting of dry mouth, dry eye, blurry vision, tachycardia, constipation, urine retention, impaired vision, constipation, nausea, cramping, reduced urinary voiding, flushed skin, fever, reduced sweating, cardiac arrhythmia, dizziness, lightheadedness, headache, drowsiness, confusion, reduced concentration, brain fog, euphoria, elevated mood, hallucinations, agitation, irritability, sensory disturbances, blurry vision, brain fog, and combinations thereof.

[0140] In some aspects, the plasma C(minimum) concentration of the R-THP is greater than or equal to about 25 ng / ml after the administration. In some aspects, the plasma concentration rate of rise of the R-THP is less than or equal to about 10 ng / ml / hr after the administration. In some aspects, the area under the curve (AUC) plasma concentration of the R-THP is about800 to about 1200 ng*hr / ml after the administration. In some aspects, wherein after the administration the R-THP has: a plasma C(minimum) concentration of greater than or equal to about 25 ng / ml; a plasma concentration rate of rise of less than or equal to about 10 ng / ml / hr; and an area under the curve (AUC) plasma concentration of about 800 to about 1200 ng*hr / ml.

[0141] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

[0142] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

[0143] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is a human patient aged 65 years or older.

[0144] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / ormagnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is a human patient aged 65 years or older.

[0145] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 10-20 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70-80 mg.

[0146] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 10-20 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70-80 mg.

[0147] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fasted state.

[0148] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinicacetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fasted state.

[0149] In some aspects, the present disclosure provides a A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fed state.

[0150] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fed state.

[0151] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising: administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(minimum) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0152] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising: administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / ormagnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(minimum) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0153] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising: administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(trough) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0154] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising: administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(trough) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0155] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein an efficacious dose of the muscarinic acetylcholine receptor inhibitor is reached within 30 days after administration of the muscarinic acetylcholine receptor inhibitor.

[0156] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein an efficacious dose of the muscarinic acetylcholine receptor inhibitor is reached within 30 days after administration of the muscarinic acetylcholine receptor inhibitor.

[0157] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

[0158] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

[0159] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movementdisorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the composition demonstrates an area under the curve (AUC) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

[0160] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the composition demonstrates an area under the curve (AUC) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

[0161] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

[0162] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein themuscarinic acetylcholine receptor inhibitor demonstrates a C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

[0163] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

[0164] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

[0165] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the muscarinic acetylcholine receptor inhibitor demonstrates a plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

[0166] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the methodcomprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the muscarinic acetylcholine receptor inhibitor demonstrates a plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

[0167] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

[0168] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

[0169] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective toreduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition demonstrates an area under the curve (AUC) plasma ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

[0170] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition demonstrates an area under the curve (AUC) plasma ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

[0171] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(minimum) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

[0172] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition provides an invivo plasma profile, and wherein the C(minimum) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

[0173] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(trough) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

[0174] In some aspects, the present disclosure provides a muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(trough) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.BRIEF DESCRIPTION OF THE FIGURES

[0175] Figure 1 is a graph depicting results of an assay measuring agonist activity of compound (5)-bethanechol chloride ((5)-BTC) toward the human Ml muscarinic receptor in the presence of (7?)-trihexyphenidyl-HCl ((R)-THP), as described in more detail in Example 5.

[0176] Figure 2 is a graph depicting changes in the EC50 of (5)-BTC toward the human Ml muscarinic receptor by the addition of (R)-THP, as described in more detail in Example 5.

[0177] Figure 3 is a graph depicting the concentration of (5)-bethanechol in rat plasma, brain tissue, and cerebrospinal fluid after a single oral dose, as described in more detail in Example 7.

[0178] Figure 4 is a graph depicting the ratio of (5)-bethanechol in brain tissue compared to plasma of a rat after a single oral dose, as described in more detail in Example 7.

[0179] Figure 5 is a graph depicting the effects of different forms of trihexyphenidyl on haloperidol-induced catalepsy in rats at 30 minutes after injection, as described in more detail in Example 9.

[0180] Figure 6 is a graph depicting the efficacy of (R)-THP and racemic THP in the haloperidol-induced catalepsy assay at different doses, as described in more detail in Example 9.

[0181] Figures 7A-7C are graphs depicting the potency and efficacy of THP alone (Figure 7A), BTC alone (Figure 7B), and THP in combination with BTC (Figure 7C) on contractions induced by electrical field stimulation (EFS) in guinea pig ileum myenteric plexus-longitudinal muscle (MPLM) strips, as described in more detail in Example 10.

[0182] Figure 8 is a graph depicting the effects of racemic THP alone, racemic BTC alone, and racemic THP administered in combination with racemic BTC on tear production, as described in more detail in Example 11.

[0183] Figures 9A-9F are a series of graphs depicting the 95% confidence interval of each treatment group from Figure 8, as described in more detail in Example 11. Figure 9A shows the THP alone treatment group. Figure 9B shows the 1:1 THP: BTC combination treatment group. Figure 9C shows the 1:1: THP: BTC staggered dosage treatment group. Figure 9D shows the 1:3 THP: BTC combination treatment group. Figure 9E shows the 1:5 THP: BTC combination treatment group. Figure 9F shows the BTC alone treatment group.

[0184] Figures 10A and 10B are graphs depicting the plasma THP concentration (ng / mL) (Figure 10A) and plasma BTC concentration (ng / mL) (Figure 10B) in dogs when administered THP alone, BTC alone, and different ratios of THP: BTC, as explained in more detail in Example 12.

[0185] Figure 11 is a graph depicting the plasma exposure levels of racemic-THP monotherapy compared to racemic-THP:racemic-BTC combination therapy, as explained in more detail in Example 13.

[0186] Figures 12A and 12B are graphs depicting the plasma THP concentration (ng / mL) and visual analog scale (VAS), a common clinical measure of dizziness, in human subjects, when 9 mg THP immediate release is administered once (Figure 12A), and when 3 mg THPadministered 3 times sequentially at 0 hours, 2 hours, and 4 hours (Figure 12B), as explained in more detail in Example 14.

[0187] Figures 13A and 13B are graphs depicting the plasma concentration of racemic THP (Figure 13 A, labeled as PK) and the plasma concentration of (R)-THP (Figure 13B, labeled as PK) (ng / mL) after administration of racemic THP in human subjects, and also shows a quantitative measure of dizziness using the visual analog scale (VAS, labeled as PD), as explained in more detail in Example 14.

[0188] Figures 14A and 14B are graphs depicting the enantiomer plasma exposure of R-THP and S-THP in humans at 0.5 hours (Figure 14A), and at 9 hours (Figure 14B).

[0189] Figure 15 is a graph depicting the enantiomer plasma exposure of R- THP as a fraction of total THP in dogs after dosing oral and IV.

[0190] Figure 16 is a series of graphs showing the metabolite profile of R- THP, S-THP, and Racemic THP after incubation in human liver microsomes at 30 minutes and 60 minutes.

[0191] Figure 17 is a graph depicting the efficacy of (R)-THP, (5)-THP, and racemic THP in a haloperidol-induced catalepsy assay at different doses, as described in more detail in Example 17.

[0192] Figures 18A and 18B are graphs depicting the plasma THP concentration (ng / mL) and visual analog scale (VAS), a common clinical measure of dizziness, in younger patients (Figure 18A), and older patients (Figure 18B), as explained in more detail in Example 18.

[0193] Figure 19 is a graph depicting the plasma concentration of THP and BTC after administration of simulated sustained release THP (5 mg administered 3 times, with 2 hours between doses) monotherapy and simulated sustained release racemic THP and 90 mg BTC combination therapy, over 24 hours.

[0194] Figure 20 is a graph depicting the plasma concentration of R- THP after administration of simulated sustained release racemic THP (5 mg administered 3 times, with 2 hours between doses), simulated sustained release racemic THP and 50 mg BTC combination therapy, simulated sustained release racemic THP and 90 mg BTC combination therapy, and simulated sustained release racemic THP and 100 mg BTC (50 mg administered 2 times, with 2 hours between doses) over twenty four hours.

[0195] Figure 21 is a graph depicting the mean change from baseline of pupil diameter (mm) in healthy human volunteers after administration of simulated sustained release racemic THP(5 mg administered 3 times, with 2 hours between doses), simulated sustained release racemic THP and 50 mg BTC combination therapy, simulated sustained release racemic THP and 90 mg BTC combination therapy, and simulated sustained release racemic THP in combination with 100 mg BTC (50 mg administered 2 times, with 2 hours between doses) over five days of dosing.

[0196] Figure 22 is a graph depicting the change in tear production in healthy human volunteers after administration of simulated sustained release racemic THP (5 mg administered 3 times, with 2 hours between doses), simulated sustained release racemic THP and 50 mg BTC combination therapy, simulated sustained release racemic THP and 90 mg BTC combination therapy, and simulated sustained release racemic THP in combination with 100 mg BTC (50 mg administered 2 times, with 2 hours between doses) over five days of dosing.

[0197] Figure 23 is a graph depicting the change in bowel movement quality in healthy human volunteers after administration of simulated sustained release racemic THP (5 mg administered 3 times, with 2 hours between doses), simulated sustained release racemic THP and 50 mg BTC combination therapy, simulated sustained release racemic THP and 90 mg BTC combination therapy, and simulated sustained release racemic THP in combination with 100 mg BTC (50 mg administered 2 times, with 2 hours between doses) over five days of dosing.

[0198] Figure 24 is a graph depicting the plasma exposure ratio of BTC: R-THP over 24 hours in healthy human volunteers following administration of simulated sustained release racemic THP and 50 mg BTC combination therapy, and simulated sustained release R-THP and 90 mg BTC combination therapy over five days of dosing.

[0199] Figure 25 is a graph depicting the percent of R-THP released in vitro over 24 hours of sustained release R-THP formulation 1, sustained release R-THP formulation 2, and sustained release R-THP formulation 3 compared to commercially available racemic THP.

[0200] Figure 26 is a graph depicting the percent of BTC released in vitro over 24 hours of sustained release BTC compared to commercially available BTC.

[0201] Figure 27A is a graph depicting the plasma concentration (ng / mL) of R-THP after administration of 5 mg R-THP in sustained release R-THP formulation 1 in a fasted state. Figure 27B is a graph depicting the plasma concentration (ng / mL) of R-THP after administration of 5 mg R-THP in sustained release R-THP formulation 2 in a fasted state.Figure 27 C is a graph depicting the plasma concentration (ng / mL) of R-THP after administration of 5 mg R-THP in sustained release R-THP formulation 3 in a fasted state.

[0202] Figure 28A is a graph depicting the fold change of R-THP absorption after administration of a single dose of 5 mg R-THP in either sustained release R-THP formulation 2 or sustained release R-THP formulation 3 in a fed state, normalized to the same formulation dosed in a fasted state. Figure 28B is a graph depicting the fold change of BTC absorption after administration of a single dose of 5 mg of sustained release BTC in combination with either R-THP formulation 2 or R-THP formulation 3 in a fed state, normalized to the same dosing paradigm in a fasted state.

[0203] Figure 29A is a graph depicting the BTC: R-THP Ratio after administering 5 mg R-THP in sustained release R-THP formulation 2 in combination with sustained release BTC or in sustained release R-THP formulation 3 in combination with sustained release BTC in a fasted state. Figure 29B is a graph depicting the BTC: R-THP Ratio after administration of 5 mg R-THP in sustained release R-THP formulation 2 in combination with sustained release BTC or in sustained release R-THP formulation 3 in combination with sustained release BTC in a fed state.

[0204] Figure 30A is a graph depicting the AUC (ng*hr / mL) by subject after administering R-THP and BTC at a 1:5 ratio (R-THP: BTC) on a titration schedule for four weeks. Figure 30B is a graph depicting the AUC (ng*hr / mL) by subject after administering R-THP and BTC at a 1:10 ratio (R-THP: BTC) on a titration schedule for four weeks.DETAILED DESCRIPTION

[0205] The invention provides therapeutic methods, pharmaceutical compositions, and unit dose formulations for treating movement disorders, such as using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator to treat dystonia. Use of the muscarinic acetylcholine receptor inhibitor in combination with the muscarinic acetylcholine receptor activator reduces the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, and also provides the further benefit of permitting a higher dose of muscarinic acetylcholine receptor inhibitor to be administered to the patient while maintaining a side effect profile that is tolerable for patients. The practice of the present invention employs, unless otherwise indicated, conventional techniques of organic chemistry, pharmacology, molecular biology (including recombinant techniques), cell biology, biochemistry, and immunology. Such techniques are explained inthe literature, such as in “Comprehensive Organic Synthesis” (B. M. Trost & I. Fleming, eds., 1991-1992); “Handbook of experimental immunology” (D. M. Weir & C. C. Blackwell, eds.); “Current protocols in molecular biology” (F. M. Ausubel et al., eds., 1987, and periodic updates); and “Current protocols in immunology” (J. E. Coligan etal., eds., 1991).

[0206] Various aspects of the invention are set forth below in sections; however, aspects of the invention described in one particular section are not to be limited to any particular section. Further, when a variable is not accompanied by a definition, the previous definition of the variable controls.Definitions

[0207] Compounds of the present invention include those described generally herein, and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. These definitions apply regardless of whether a term is used by itself or in combination with other terms, unless otherwise indicated. Hence, the definition of “alkyl” applies to “alkyl” as well as the “alkyl” portions of “-O-alkyl” etc. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry”, 5thEd., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001.

[0208] The term “aliphatic” or “aliphatic group”, as used herein, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic hydrocarbon or bicyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as “cycloaliphatic”), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms. In some embodiments, “cycloaliphatic” refers to a monocyclic C3-C6 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, thathas a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0209] As used herein, the term “bicyclic ring” or “bicyclic ring system” refers to any bicyclic ring system, i.e., carbocyclic or heterocyclic, saturated or having one or more units of unsaturation, having one or more atoms in common between the two rings of the ring system. Thus, the term includes any permissible ring fusion, such as ortAo-fused or spirocyclic. As used herein, the term “heterobicyclic” is a subset of “bicyclic” that requires that one or more heteroatoms are present in one or both rings of the bicycle. Such heteroatoms may be present at ring junctions and are optionally substituted, and may be selected from nitrogen (including N-oxides), oxygen, sulfur (including oxidized forms such as sulfones and sulfonates), phosphorus (including oxidized forms such as phosphates), boron, etc. In some embodiments, a bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. As used herein, the term “bridged bicyclic” refers to any bicyclic ring system, i.e., carbocyclic or heterocyclic, saturated or partially unsaturated, having at least one bridge. As defined by IUPAC, a “bridge” is an unbranched chain of atoms or an atom or a valence bond connecting two bridgeheads, where a “bridgehead” is any skeletal atom of the ring system which is bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, a bridged bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include those groups set forth below where each group is attached to the rest of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise specified, a bridged bicyclic group is optionally substituted with one or more substituents as set forth for aliphatic groups.Additionally or alternatively, any substitutable nitrogen of a bridged bicyclic group is optionally substituted. Exemplary bicyclic rings include:

[0210] Exemplary bridged bicyclics include:

[0211] The term “lower alkyl” refers to a Ci-4 straight or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0212] The term “heteroatom” means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quatemized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro-2J / -pyrrolyl), NH (as in pyrrolidinyl) or NR (as in N-substituted pyrrolidinyl)).

[0213] The term “unsaturated,” as used herein, means that a moiety has one or more units of unsaturation.

[0214] As used herein, the term “bivalent Ci-s (or Ci-e) saturated or unsaturated, straight or branched, hydrocarbon chain”, refers to bivalent alkylene, alkenylene, and alkynylene chains that are straight or branched as defined herein.

[0215] The term “alkylene” refers to a bivalent alkyl group. An “alkylene chain” is a polymethylene group, i.e., -(CH2)n- wherein n is a positive integer, preferably from 1 to 6,from 1 to 4, from 1 to 3, from 1 to 2, or from 2 to 3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group.

[0216] The term “-(Co alkylene)-“ refers to a bond. Accordingly, the term “-(Co-3 alkylene)-“ encompasses a bond (i.e., Co) and a -(C1-3 alkylene)- group.

[0217] The term “alkenylene” refers to a bivalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group.

[0218] The term “halogen” means F, Cl, Br, or I.

[0219] The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic or bicyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. The term “aryl” may be used interchangeably with the term “aryl ring.” In some aspects, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like.

[0220] The terms “heteroaryl” and “heteroar-,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 it electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar-”, as used herein, also include groups in which a heteroaromatic ring is fused to one or morearyl, cycloaliphatic, or heterocyclyl rings, where unless otherwise specified, the radical or point of attachment is on the heteroaromatic ring or on one of the rings to which the heteroaromatic ring is fused. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 47 / quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, and tetrahydroisoquinolinyl. A heteroaryl group may be mono- or bicyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted.

[0221] As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7-10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term “nitrogen” includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3, 4-di hydro-27 / pyrrolyl), NH (as in pyrrolidinyl), or+NR (as in TV-substituted pyrrolidinyl).

[0222] A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, 2-oxa-6-azaspiro[3.3]heptane, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 377-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. A heterocyclyl group may be mono- orbicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted.

[0223] As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.

[0224] As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position.Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in some aspects, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0225] Each optional substituent on a substitutable carbon is a monovalent substituent independently selected from halogen; -(CEbjo 4R0; -(CEbjo 4OR0; -0(CH2)o-4R°, -0-(CH2)o-4C(O)OR°; -(CH2)O 4CH(ORC)2; -(CH2)O 4SR0; -(CH2)o-4Ph, which may be substituted with R°; -(CH2)o40(CH2)o! Ph which may be substituted with R°; -CH=CHPh, which may be substituted with R°; -(CH2)o 40(CH2)o 1 -pyridyl which may be substituted with R°; -NO2; -CN; -N3; (CH2)O4N(RO)2; -(CH2)O4N(RO)C(O)R°; -N(R°)C(S)R°; -(CH2)O 4N(RO)C(O)NR°2; N(RO)C(S)NR°2; -(CH2)O4N(RO)C(O)OR°; -N(R°)N(R°)C(O)R°;N(R°)N(RO)C(O)NRO2; N(R°)N(R°)C(O)OR°; -(CH2)O4C(O)RO; -C(S)R°; -(CH2)O4C(O)ORO; -(CH2)O 4C(O)SRC; (CH2)O ^C(O)OSiR°3; -(CH2)o4OC(O)R°; -OC(0)(CH2)o 4SR-, SC(S)SR°; -(CH2)O4SC(O)R°; -(CH2)O4C(O)NRO2; -C(S)NRO2; -C(S)SR°; -SC(S)SR°, (CH2)O4OC(O)NR°2; C(O)N(OR°)R°; -C(O)C(O)R°; -C(O)CH2C(O)RO; -C(NOR°)R°; (CH2)o 4SSR0; -(CH2)o 4S(O)2R°; -(CH2)o4S(O)2ORO; -(CH2)o4OS(O)2RO; -S(O)2NR°2; -S(O)(NR°)R°; -S(O)2N=C(NRO2)2; (CH2)O 4S(O)RC; N(RO)S(O)2NR°2; -N(R°)S(O)2R°; -N(0R°)R°; -C(NH)NRO2; -P(O)2RO; P(O)RO2; OP(O)RO2; -OP(O)(ORO)2; SiR°3; - (Ci— 4 straight or branched alkylene)O-N(R°)2; or -(Ci-4 straight or branched alkylene)C(O)O-N(R°)2.

[0226] Each R° is independently hydrogen, Ci-6 aliphatic, -CH2PI1, -0(CH2)o iPh, -CH2-(5-6 membered heteroaryl ring), or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R°, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted by a divalent substituent on a saturated carbon atom of R° selected from =0 and =S; or each R° is optionally substituted with a monovalent substituent independently selected from halogen, -(CH2)o-2R*, -(haloR*), -(CH2)o 2OH, - (CH2)o 2OR*, -(CH2)O2CH(OR*)2; O(haloR’), -CN, -N3, -(CH2)o2C(O)R*, -(CH2)o2C(O)OH, -(CH2)O2C(O)OR*, -(CH2)O2SR*, -(CH2)O 2SH, -(CH2)o 2NH2, -(CH2)o2NHR*, - (CH2)o2NR*2, -NO2, -SiR*3, -OSiR*3, C(O)SR*. -(Ci^i straight or branched alkylene)C(O)OR*, or-SSR*.

[0227] Each R* is independently selected from Ci-4 aliphatic, -CH2PI1, -0(CH2)o iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R* is unsubstituted or where preceded by halo is substituted only with one or more halogens; or wherein an optional substituent on a saturated carbon is a divalent substituent independently selected from =0, =S, =NNR =NNHC(0)R*, =NNHC(0)0R*, =NNHS(O)2R*, =NR*, =N0R*, -or a divalent substituent bound to vicinal substitutable carbons of an “optionally substituted” group is -O(CR*2)23O-, wherein each independent occurrence of R* is selected from hydrogen, C1-6 aliphatic or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0228] When R* is C1-6 aliphatic, R* is optionally substituted with halogen, -R*, (haloR*), OH, -OR’, -O(haloR’), -CN, -C(O)OH, -C(O)OR*, -NH2, -NHR*, -NR*2, or -NO2, wherein each R* is independently selected from Ci-4 aliphatic, -CEEPh, -0(CH2)o iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatomsindependently selected from nitrogen, oxygen, or sulfur, and wherein each R* is unsubstituted or where preceded by halo is substituted only with one or more halogens.

[0229] An optional substituent on a substitutable nitrogen is independently -R1', -NR1'?, -C(NH)NR / 2, or -N(R'f')S(O)2R1'; wherein each R1' is independently hydrogen, Ci-6 aliphatic, unsubstituted -OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, two independent occurrences of R \ taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein when R1' is Ci-6 aliphatic, R1' is optionally substituted with halogen, -R*, (haloR*), OH, -OR’, -O(haloR’), -CN, -C(O)OH, -C(O)OR’, -NH2, -NHR’, -NR’2, or -NO2, wherein each R* is independently selected from Ci-4 aliphatic, -CH2Ph, -0(CH2)o iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R* is unsubstituted or where preceded by halo is substituted only with one or more halogens.

[0230] As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge etal., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemi sulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate,maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like.

[0231] Further, acids which are generally considered suitable for the formation of pharmaceutically useful salts from basic pharmaceutical compounds are discussed, for example, by P. Stahl et aL, Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley-VCH; S. Berge et al., Journal of Pharmaceutical Sciences (1977) 66(1): 1-19; P. Gould, International J. of Pharmaceutics (1986) 33: 201-217; Anderson etal., The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, D. C. on their website).

[0232] Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N (Ci 4alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate.

[0233] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. The invention includes compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a13C- or14C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention.

[0234] Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods known to those skilled in the art, suchas, for example, by chromatography and / or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher’s acid chloride), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Alternatively, a particular enantiomer of a compound of the present invention may be prepared by asymmetric synthesis. Still further, where the molecule contains a basic functional group (such as amino) or an acidic functional group (such as carboxylic acid) diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means known in the art, and subsequent recovery of the pure enantiomers.

[0235] Individual stereoisomers of the compounds of the invention may, for example, be substantially free of other isomers, or may be admixed, for example, as racemates or with all other, or other selected, stereoisomers. Chiral center(s) in a compound of the present invention can have the S or R configuration as defined by the IUPAC 1974 Recommendations. Further, to the extent a compound described herein may exist as an atropisomer (e.g., substituted biaryls), all forms of such atropisomer are considered part of this invention.

[0236] Chemical names, common names, and chemical structures may be used interchangeably to describe the same structure. If a chemical compound is referred to using both a chemical structure and a chemical name, and an ambiguity exists between the structure and the name, the structure predominates. It should also be noted that any carbon as well as heteroatom with unsatisfied valences in the text, schemes, examples and tables herein is assumed to have the sufficient number of hydrogen atom(s) to satisfy the valences.

[0237] The terms “a” and “an” as used herein mean “one or more” and include the plural unless the context is inappropriate.

[0238] The term “alkyl” refers to a saturated straight or branched hydrocarbon, such as a straight or branched group of 1-12, 1-10, or 1-6 carbon atoms, referred to herein as C1-C12 alkyl, C1-C10 alkyl, and Ci-Ce alkyl, respectively. Exemplary alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, 2-methyl-l -propyl, 2-methyl-2-propyl, 2-methyl-1 -butyl, 3 -methyl- 1 -butyl, 2-methyl-3 -butyl, 2,2-dimethyl-l -propyl, 2-methyl-l -pentyl, 3-m ethyl- 1 -pentyl, 4-methyl-l -pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-l -butyl, 3,3-dimethyl-l-butyl, 2-ethyl-l -butyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, etc.

[0239] The term “cycloalkyl” refers to a monovalent saturated cyclic, bicyclic, or bridged cyclic (e.g., adamantyl) hydrocarbon group of 3-12, 3-8, 4-8, or 4-6 carbons, referred to herein, e.g., as “C3-C6 cycloalkyl,” derived from a cycloalkane. Exemplary cycloalkyl groups include cyclohexyl, cyclopentyl, cyclobutyl, and cyclopropyl. The term “cycloalkylene” refers to a bivalent cycloalkyl group.

[0240] The symbol “ ” indicates a point of attachment.

[0241] When any substituent or variable occurs more than one time in any constituent or the compound of the invention, its definition on each occurrence is independent of its definition at every other occurrence, unless otherwise indicated.

[0242] One or more compounds of the invention may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and it is intended that the invention embrace both solvated and unsolvated forms. “Solvate” means a physical association of a compound of this invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. “Solvate” encompasses both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include ethanolates, methanolates, and the like. “Hydrate” is a solvate wherein the solvent molecule is H2O.

[0243] As used herein, the terms “subject” and “patient” are used interchangeable and refer to organisms to be treated by the methods of the present invention. Such organisms preferably include, but are not limited to, mammals e.g., murines, simians, equines, bovines, porcines, canines, felines, and the like), and most preferably includes humans.

[0244] The term “IC50” is art-recognized and refers to the concentration of a compound that is required to achieve 50% inhibition of the target.

[0245] The term “EC50” is art-recognized and refers to the concentration of a compound that is required to achieve 50% activation of the target.

[0246] As used herein, the term “effective amount” or “amount effective” are used interchangeably and refer to the amount of a compound sufficient to effect beneficial ordesired results (e.g., a therapeutic, ameliorative, inhibitory or preventative result). An effective amount can be administered in one or more administrations, applications or dosages and is not intended to be limited to a particular formulation or administration route. As used herein, the terms “treat,” “treating,” and “treatment” include any effect, e.g., lessening, reducing, modulating, ameliorating or eliminating, that results in the improvement of the condition, disease, disorder, and the like, or ameliorating a symptom thereof.

[0247] As used herein, the term “pharmaceutical composition” refers to the combination of an active agent with a carrier, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo or ex vivo.

[0248] As used herein, the term “pharmaceutically acceptable carrier” refers to any of the standard pharmaceutical carriers, such as a phosphate buffered saline solution, water, emulsions (e.g., such as an oil / water or water / oil emulsions), and various types of wetting agents. The compositions also can include stabilizers and preservatives. For examples of carriers, stabilizers and adjuvants, see e.g., Martin, Remington’s Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA

[1975] ,

[0249] For therapeutic use, salts of the compounds of the present invention are contemplated as being pharmaceutically acceptable. However, salts of acids and bases that are non-pharmaceutically acceptable may also find use, for example, in the preparation or purification of a pharmaceutically acceptable compound.

[0250] In addition, when a compound of the invention contains both a basic moiety (such as, but not limited to, a pyridine or imidazole) and an acidic moiety (such as, but not limited to, a carboxylic acid) zwitterions (“inner salts”) may be formed. Such acidic and basic salts used within the scope of the invention are pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts. Such salts of the compounds of the invention may be formed, for example, by reacting a compound of the invention with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in an aqueous medium followed by lyophilization.

[0251] As used herein, the term “THP” refers to trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, “Rac-THP” or “Racemic-THP” refer to racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, “(A)-THP” or “R-THP” refers to (A)-trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, “(5)-THP” or “S-THP” refers to (5)-trihexyphenidyl or a pharmaceutically acceptablesalt thereof. As used herein, the term “BTC” refers to bethanechol or a pharmaceutically acceptable salt thereof. As used herein, “Rac-BTC” or “Racemic-BTC” refer to racemic bethanechol or a pharmaceutically acceptable salt thereof. As used herein, “(A)-BTC” or “R-BTC” refers to (A)-bethanechol or a pharmaceutically acceptable salt thereof. As used herein, “(5)-BTC” or “S-BTC” refers to (5)-bethanechol or a pharmaceutically acceptable salt thereof.

[0252] As used herein, the terms “magnitude” and “severity” are used interchangeably.

[0253] As used herein, the term “C(minimum)” refers to the lowest detectable concentration of a compound in the subject’s serum or plasma during an interval of time between the administration of two or more doses of a compound.

[0254] As used herein, the term “C(maximum)” refers to the highest detectable concentration of a compound in the subject’s serum or plasma after administration of a compound.

[0255] As used herein, the term “C(trough)” refers to the concentration of a compound in the subject’s serum or plasma immediately before the next dose of the compound is administered.

[0256] Throughout the description, where compositions are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.

[0257] As a general matter, compositions specifying a percentage are by weight unless otherwise specified.I. Therapeutic Methods

[0258] The invention provides therapeutic methods using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator. The therapeutic methods are useful for treating a movement disorder. Various aspects and embodiments of the therapeutic methods are described in the sections below. The sections are arranged for convenience and information in one section is not to be limited to that section, but may be applied to methods in other sections.A. First Therapeutic Method

[0259] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

[0260] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

[0261] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

[0262] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

[0263] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

[0264] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinicacetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is bethanechol or pharmaceutically acceptable salt thereof.

[0265] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is bethanechol or pharmaceutically acceptable salt thereof.

[0266] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is bethanechol or pharmaceutically acceptable salt thereof.

[0267] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is bethanechol or pharmaceutically acceptable salt thereof.

[0268] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequencyof at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is bethanechol or pharmaceutically acceptable salt thereof.

[0269] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0270] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0271] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein themuscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0272] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0273] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0274] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0275] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0276] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0277] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0278] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii)a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0279] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0280] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0281] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinicacetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0282] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / ?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0283] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / ?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0284] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) amuscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0285] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0286] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0287] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0288] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:20.

[0289] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:10.

[0290] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0291] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / ?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0292] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0293] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii)a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0294] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:10.

[0295] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0296] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor,wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0297] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0298] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0299] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:10.

[0300] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:10.

[0301] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0302] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor,wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0303] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0304] One aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:10.

[0305] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reducethe frequency and magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:10.

[0306] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0307] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0308] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, aprocholinergic agent, and an acetylcholinesterase inhibitor in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1: 1.1 to about 1:10.

[0309] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio of about 1:1.1 to about 1:20.

[0310] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is ( / ?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered at a weight ratio greater than 1: 1 and wherein the muscarinic acetylcholine receptor activator is administered in excess of the muscarinic acetylcholine receptor inhibitor.

[0311] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein themuscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl or pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or pharmaceutically acceptable salt thereof, and wherein a greater amount of the muscarinic acetylcholine receptor activator is administered compared to the amount of the muscarinic acetylcholine receptor inhibitor administered.

[0312] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a muscarinic receptor activator, wherein the amount of muscarinic acetylcholine receptor inhibitor is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the muscarinic receptor activator.

[0313] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the amount of the ( / ?)-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the muscarinic receptor activator.

[0314] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the dose of ( / ?)-trihexyphenidyl or pharmaceutically acceptable salt thereof is about 50% less than the dose of racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof, and wherein the (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the muscarinic receptor activator.

[0315] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the amount of the racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the muscarinic receptor activator.

[0316] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of the racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the muscarinic receptor activator.

[0317] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a muscarinic receptor activator, wherein if the subject is administered a standard, monotherapy dose of a muscarinic acetylcholine receptor inhibitor, which would be known to those in the art, in combination with a muscarinic receptor activator, the subject would experience increased frequency, increased magnitude, and / or more severe adverse effects compared to a subject who was administered a standard, monotherapy dose of a muscarinic acetylcholine receptor inhibitor.

[0318] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein if the subject is administered a standard, monotherapy dose of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, which would be known to those in the art, in combination with a muscarinic receptor activator, the subject would experience increased frequency, increased magnitude, or more severe adverse effects compared to a subject who was administered a standard, monotherapy dose of (R)-trihexyphenidyl alone.

[0319] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein if the subject is administered a standard, monotherapy dose of racemic-trihexyphenidyl, which would be known to those in the art, or a pharmaceutically acceptable salt thereof in combination with a muscarinic receptor activator, the subject would experience increased frequency, increased magnitude, or more severe adverse effects compared to a subject who was administered a standard, monotherapy dose of racemic-trihexyphenidyl alone.

[0320] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein if the subject is administered a standard, monotherapy dose of a muscarinic acetylcholine receptor inhibitor, which would be known to those in the art, in combination with a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, the subject would experience increased frequency, increased magnitude, or more severe adverse effects compared to a subject who was administered a standard dose of a muscarinic acetylcholine receptor inhibitor.

[0321] The method may be characterized by additional features, such as the identity of the muscarinic acetylcholine receptor inhibitor, identity of the muscarinic acetylcholine receptor activator, order of administration, and other features as described herein in more detail.Muscarinic Acetylcholine Receptor Inhibitor

[0322] The method may be characterized by the identity of the muscarinic acetylcholine receptor inhibitor. For example, in some aspects, the muscarinic acetylcholine receptor inhibitor distributes to the central nervous system and the peripheral nervous system in the patient.

[0323] In some aspects, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl. In some aspects, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl hydrochloride.

[0324] In some aspects, the muscarinic acetylcholine receptor inhibitor is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is racemic trihexyphenidyl. In some aspects, the muscarinic acetylcholine receptor inhibitor is racemic trihexyphenidyl hydrochloride.

[0325] In some aspects, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl. In some aspects, the muscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl hydrochloride.

[0326] In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-trihexyphenidyl having a stereochemical purity of at least 90% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 98% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-trihexyphenidyl having a stereochemical purity of at least 99% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

[0327] In some aspects, (a) the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof and (b) the muscarinic acetylcholine receptor inhibitor is (A)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

[0328] In some aspects, the muscarinic acetylcholine receptor inhibitor is Aclidinium bromide, Aclidinium bromide / formoterol, Acotiamide, AH 9700, Alvameline, AQRA 721, AQRA 741, AZD 9164, BIBN 99, CEB 1957, Clozapine, Darenzepine, Darifenacin, Darotropium bromide, Dextro-mequitamium iodide, Ebeinone, Esoxybutynin, Espatropate, Ethopropazine, Fesoterodine, Glycopyrrolate / indacaterol, Glycopyrronium bromide, GSK 1160724, GSK 202405, GSK 573719, GSK 656398, GSK 961081, GYKI 46903, Homatropine methylbromide, Imidafenacin, glycopyrrolate, Ipratropium bromide, Ipratropium bromide / xylometazoline, J 104129, J 106366, L 696986, LAS 35201, Levosalbutamol / ipratropium inhalation solution, Liriodenine, LK 12, Mequitamium iodide, Methantheline, Methantheline bromide, Methscopolamine bromide, N-butylscopolamine, N-methyl-4-piperidyl benzylate, N-methylatropine, NPC 14695, NX 303, Otenzepad, Oxybutynin-Labopharm, Oxybutynin, Oxybutynin chloride, Oxybutynin intravesical, Oxybutynin transdermal, Oxybutynin transdermal, Oxybutynin transdermal gel, Oxvbutynin transmucosal, Oxybutynin vaginal, PG 1000, Pirenzepine ophthalmic, Pirmenol, PNU 200577, Promethazine / hydrocodone / paracetamol, Propantheline, Propantheline bromide, Propiverine, PSD 506, PTAC, QAT 370, FF2-Nuada, Revatropate, Rispenzepine, RL 315535, RO 465934, SCH 211803, SCH 57790, Scopolamine intranasal, Scopolamine transmucosal, Secoverine, S-ET 126, Sintropium bromide, Solifenacin, Solifenacin / tamsulosin, SVT 40776, TD 6301, Telenzepine, Temiverine, Tiotropium bromide, Tolterodine, Tolterodine / tamsulosin, Tropenzilium, Trospium chloride, V 0162,YM 35636, YM 46303, YM 53705, YM 58790, Zamifenacin, atropine sulfate monohydrate, scopolamine, benztropine mesylate, or ethopropazine hydrochloride, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor inhibitor is biperiden. In some aspects, the muscarinic acetylcholine receptor inhibitor is cycrimine. In some aspects, the muscarinic acetylcholine receptor inhibitor is procyclidine.

[0329] In some aspects, the method of using the muscarinic acetylcholine receptor inhibitor comprises administering a sustained release pharmaceutical composition comprising the muscarinic acetylcholine receptor inhibitor. Further aspects of pharmaceutical compositions for use in the invention are disclosed herein.B. Second Therapeutic Method

[0330] Another aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a therapeutically effective amount of a muscarinic acetylcholine receptor inhibitor selected from (A)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess or a pharmaceutically acceptable salt thereof and (ii) a muscarinic acetylcholine receptor activator, to thereby treat the movement disorder. In some aspects, the muscarinic acetylcholine receptor activator is administered to the patient in an amount effective to reduce side effects of the muscarinic acetylcholine receptor inhibitor.

[0331] The method may be characterized by additional features, such as the amount of muscarinic acetylcholine receptor activator administered to the patient, the identity of the muscarinic acetylcholine receptor activator, order of administration, and other features as described herein in more detail.

[0332] In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered a starting dose of 2.5 mg (A)-THP per day without the bethanechol. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered a starting dose of 2.5 mg (A)-THP per day and 12.5 mg of bethanechol per day. In some aspects, the starting dose is administered for about 7 days. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered 5 mg of (A)-THP per day and 25 mg of bethanechol per day for about 7 days after being administered the starting dose for 7 days. In some aspects, themuscarinic acetylcholine receptor inhibitor is (?)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered 10 mg of (?)-THP per day and 50 mg of bethanechol per day for about 7 days after being administered 5 mg of (?)-THP per day and 25 mg per day of bethanechol for about 7 days. In some aspects, the muscarinic acetylcholine receptor inhibitor is (?)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered 15 mg of (?)-THP per day and 75 mg of bethanechol per day after being administered 10 mg of (?)-THP per day and 50 mg of bethanechol per day for about 7 days.C. Third Therapeutic Method[0333 j Another aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor and (ii) a muscarinic acetylcholine receptor activator, to thereby treat the movement disorder.

[0334] In some aspects, the muscarinic acetylcholine receptor activator does not prevent the therapeutic benefit of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

[0335] The method may be characterized by additional features, such as the identity of the muscarinic acetylcholine receptor inhibitor, identity of the muscarinic acetylcholine receptor activator, order of administration, and other features as described herein in more detail.

[0336] In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered a starting dose of 2.5 mg (A)-THP per day without the bethanechol. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered a starting dose of 2.5 mg (A)-THP per day and 12.5 mg of bethanechol per day. In some aspects, the starting dose is administered for about 7 days. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered 5 mg of (A)-THP per day and 25 mg of bethanechol per day for about 7 days after being administered the starting dose for 7 days. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered 10 mg of (A)-THP per day and 50 mg of bethanechol per day for about 7 days after being administered 5 mg of (A)-THPper day and 25 mg per day of bethanechol for about 7 days. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-THP and the muscarinic acetylcholine receptor activator is bethanechol, and the patient is administered 15 mg of (R)-THP per day and 75 mg of bethanechol per day after being administered 10 mg of (A)-THP per day and 50 mg of bethanechol per day for about 7 days.D. Fourth Therapeutic Method

[0337] Another aspect of the invention provides a method of treating a movement disorder in a patient, wherein the method comprises administering to a patient in need thereof a single enantiomer of a muscarinic acetylcholine receptor inhibitor, wherein the enantiomer has a stereochemical purity of at least 90% enantiomeric excess.E. Fifth Therapeutic Method

[0338] In some aspects, provided is a method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the second therapeutic agent is administered to the patient in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

[0339] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of muscarinic acetylcholine receptor inhibitor is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the second therapeutic agent.

[0340] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of the ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose levelinsufficient to reach an efficacious dose if it were to be dosed in the absence of the second therapeutic agent.

[0341] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of the racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the second therapeutic agent.

[0342] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of muscarinic acetylcholine receptor inhibitor is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the second therapeutic agent, and wherein the dose of the muscarinic acetylcholine receptor inhibitor reduces the frequency, magnitude and / or severity of at least one central nervous system adverse effect when administered in combination with the second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor to reduce the frequency, magnitude and / or severity of at least one peripheral nervous system adverse effect.

[0343] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of the ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the second therapeutic agent, and wherein the dose of the ( / / (-trihexyphenidyl or pharmaceutically acceptable salt thereof reduces the frequency, magnitude and / or severity of at least one central nervous system adverse effects when administered in combination with the second therapeutic agent selected from a muscarinic acetylcholine receptor activator, aprocholinergic agent, and an acetylcholinesterase inhibitor to reduce the frequency, magnitude and / or severity of at least one peripheral nervous system adverse effects.

[0344] In some aspects, the present disclosure provides a method of treating a movement disorder in a subject in need thereof comprising administering to the subject (i) racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor, to thereby treat the movement disorder, wherein the amount of the racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an efficacious dose if it were to be dosed in the absence of the second therapeutic agent, and wherein the dose of the racemic-trihexyphenidyl or pharmaceutically acceptable salt thereof reduces the frequency, magnitude and / or severity of at least one central nervous system adverse effects when administered in combination with the second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a procholinergic agent, and an acetylcholinesterase inhibitor to reduce the frequency, magnitude and / or severity of at least one peripheral nervous system adverse effects.

[0345] In some aspects, the second therapeutic agent is a procholinergic agent. In some aspects, the second therapeutic agent is an acetylcholinesterase inhibitor. In some aspects, the second therapeutic agent is pyridostigmine, neostigmine, physostigmine, edrophonium, or a pharmaceutically acceptable salt thereof. In some aspects, the second therapeutic agent is distigmine bromide.

[0346] In some aspects, the patient does not experience any adverse side effect due to the second therapeutic agent. In some aspects, the patient does not experience any adverse side effect due to the muscarinic acetylcholine receptor activator.F. Additional Embodiments for First, Second, Third, Fourth and Fifth Therapeutic Method

[0347] Additional embodiments for the First, Second, Third, and Fourth Therapeutic Method are described herein below. These include, for example, the identity of the muscarinic acetylcholine receptor activator, therapeutic effect, administration features, dosing, identity of the movement disorder, and identity of the patient.Muscarinic Acetylcholine Receptor Activator

[0348] The method may be characterized by the identity of the muscarinic acetylcholine receptor activator. For example, in some aspects, the muscarinic acetylcholine receptor activator distributes predominately to the peripheral nervous system in the patient.

[0349] In some aspects, the muscarinic acetylcholine receptor activator is selected from acetylcholine, A 72055, AF 125, AF 150(5), AF 185, Alvameline, Amifostine, Arecoline, bethanechol, carbachol, Cevimeline, CI 1017, CMI 1145, CMI 936, CS 932, DM 71, FPL 14995, GSK 1034702, Himbacine, Itameline, KST 2818, KSI 5410, KST 5452, L 670548, L 689660, L 696986, L 705106, LY 316108, MCD 386, methacholine, Milameline, NC 111585, Nebracetam, NGX 267, Norclozapine, ORG 20091, PD 141606, PD 142505, PD 151832, PDC 008004, Pilocarpine, PTAC, RU 35963, Sabcomeline, SDZ 210086, SR 46559A, SR 96777A, Stacofylline, Talsaclidine, Tazomeline, Thiopilocarpine, Ticalopride, U 80816, Vedadidine, WAY 131256, WAY 132983, Xanomeline, YM 796, or YM 954, or a pharmaceutically acceptable salt thereof.

[0350] In some aspects, the muscarinic acetylcholine receptor activator is acetylcholine, methacholine, carbachol, pilocarpine, cevimeline, or bethanechol, or a pharmaceutically acceptable salt thereof.

[0031] In some aspects, the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor activator is bethanechol. In some aspects, the muscarinic acetylcholine receptor activator is bethanechol salt. In some aspects, the muscarinic acetylcholine receptor activator is bethanechol chloride. In some aspects, the muscarinic acetylcholine receptor inhibitor is (A)-trihexyphenidyl hydrochloride and the muscarinic acetylcholine receptor activator is bethanechol chloride.

[0352] In some aspects, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor activator is racemic bethanechol. In some aspects, the muscarinic acetylcholine receptor activator is racemic bethanechol chloride.

[0353] In some aspects, the muscarinic acetylcholine receptor activator is (5)-bethanechol or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor activator is (S)-bethanechol. In some aspects, the muscarinic acetylcholine receptoractivator is (5)-bethanechol salt. In some aspects, the muscarinic acetylcholine receptor activator is (5)-bethanechol chloride.

[0354] In some aspects, the muscarinic acetylcholine receptor activator is fS')-bethanechol having a stereochemical purity of at least 90% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor activator is (5)-bethanechol having a stereochemical purity of at least 95% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor activator is (5)-bethanechol having a stereochemical purity of at least 98% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, the muscarinic acetylcholine receptor activator is fS')-bethanechol having a stereochemical purity of at least 99% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

[0355] In some aspects, the muscarinic acetylcholine receptor activator is a (5)-bethanechol salt having a stereochemical purity of at least 90% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor activator is a fS')-bethanechol salt having a stereochemical purity of at least 95% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor activator is a (5)-bethanechol salt having a stereochemical purity of at least 98% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor activator is a (5)-bethanechol salt having a stereochemical purity of at least 99% enantiomeric excess.

[0356] In some aspects, the muscarinic acetylcholine receptor activator is a (5)-bethanechol chloride having a stereochemical purity of at least 90% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor activator is a fS')-bethanechol chloride having a stereochemical purity of at least 95% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor activator is a (5)-bethanechol chloride having a stereochemical purity of at least 98% enantiomeric excess. In some aspects, the muscarinic acetylcholine receptor activator is a fS')-bethanechol chloride having a stereochemical purity of at least 99% enantiomeric excess.

[0357] In some aspects, (a) the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof and (b) the muscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl having a stereochemical purity of at least 90% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, (a) the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof and (b) the muscarinic acetylcholine receptorinhibitor is (7?)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, (a) the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof and (b) the muscarinic acetylcholine receptor inhibitor is (?)-trihexyphenidyl having a stereochemical purity of at least 96% enantiomeric excess, or a pharmaceutically acceptable salt thereof. In some aspects, (a) the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof and (b) the muscarinic acetylcholine receptor inhibitor is (7?)-trihexyphenidyl having a stereochemical purity of at least 99% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

[0358] In some aspects, the method of using the muscarinic acetylcholine receptor activator comprises administering a sustained release pharmaceutical composition comprising the muscarinic acetylcholine receptor activator. Further aspects of pharmaceutical compositions for use in the invention are disclosed herein.

[0359] In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is 1 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 2 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 3 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 4 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 5 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 8 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 10 to 1. Insome aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 15 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 20 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 50 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 75 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 100 to 1. In some aspects, the mole ratio of (i) muscarinic acetylcholine receptor activator present in the peripheral nervous system of the patient to (ii) muscarinic acetylcholine receptor activator present in the central nervous system of the patient is at least 1,000 to 1.

[0360] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 1.1 to about 1:20. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.2 to about 1:19.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.3 to about 1: 19.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 1.4 to about 1: 19.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.5 to about 1:19.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.6 to about 1: 19.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.7 to about 1:19.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.8 to about 1:19.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.9 to about 1: 19.2. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2 to about 1:19.1.

[0361] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.1 to about 1: 19. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.2 to about 1:18.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.3 to about 1: 18.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.4 to about 1:18.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.5 to about 1:18.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.6 to about 1: 18.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.7 to about 1:18.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.8 to about 1:18.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.9 to about 1:18.2.

[0362] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3 to about 1:18.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.1 to about 1:18. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.2 to about 1: 17.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.3 to about 1:17.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.4 to about 1:17.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.5 to about 1: 17.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.6 to about 1:17.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.7 to about 1:17.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.8 to about 1: 17.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.9 to about 1:17.2.

[0363] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4 to about 1:17.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.1 to about 1:17. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.2 to about 1: 16.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.3 to about 1:16.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.4 to about 1:16.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.5 to about1: 16.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.6 to about 1:16.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.7 to about 1:16.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.8 to about 1: 16.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.9 to about 1:16.2.

[0364] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5 to about 1:16.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.1 to about 1:16. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.2 to about 1: 15.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.3 to about 1:15.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.4 to about 1:15.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.5 to about 1: 15.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.6 to about 1:15.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.7 to about 1:15.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.8 to about 1: 15.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.9 to about 1:15.2.

[0365] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6 to about 1:15.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.1 to about 1:15. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.2 to about 1: 14.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.3 to about 1:14.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.4 to about 1:14.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.5 to about 1: 14.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.6 to about 1:14.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.7 to about 1:14.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.8 to about1: 14.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6.9 to about 1:14.2.

[0366] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7 to about 1:14.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.1 to about 1:14. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.2 to about 1: 13.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.3 to about 1:13.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.4 to about 1:13.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.5 to about 1: 13.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.6 to about 1:13.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.7 to about 1:13.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.8 to about 1: 13.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7.9 to about 1:13.2.

[0367] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8 to about 1:13.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.1 to about 1:13. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.2 to about 1: 12.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.3 to about 1:12.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.4 to about 1:12.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.5 to about 1: 12.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.6 to about 1:12.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.7 to about 1:12.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.8 to about 1: 12.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8.9 to about 1:12.2.

[0368] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9 to about 1:12.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.1 to about 1:13. In some aspects, theweight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.2 to about 1: 11.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.3 to about 1: 11.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.4 to about 1: 11.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.5 to about 1: 11.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.6 to about 1: 11.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.7 to about 1:11.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.8 to about 1: 11.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9.9 to about 1: 11.2.

[0369] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 10 to about 1: 11.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:10.1 to about 1: 11. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 10.2 to about 1: 10.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:10.3 to about 1:10.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:10.4 to about 1:10.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:10.5 to about 1:10.6.

[0370] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3 to about 1:7.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.1 to about 1:6.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.2 to about 1:6.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.3 to about 1:6.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.4 to about 1:6.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.5 to about 1:6.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.6 to about 1:6.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.7 to about 1:6.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.8 to about1:6.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.9 to about 1:6.2.

[0371] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4 to about 1:6.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.1 to about 1:5.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.2 to about 1:5.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.3 to about 1:5.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.4 to about 1:5.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.5 to about 1:5.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.6 to about 1:5.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.7 to about 1:5.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.8 to about 1:5.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.9 to about 1:5.2. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5 to about 1:5.1.

[0372] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 1.1 to about 1: 10. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.2 to about 1:9.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.3 to about 1:9.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.4 to about 1:9.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.5 to about 1:9.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.6 to about 1:9.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.7 to about 1:9.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.8 to about 1:9.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:1.9 to about 1:9.2. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2 to about 1:9.1.

[0373] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.1 to about 1:9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.2 to about 1:8.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.3 to about 1:8.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.4 to about 1:8.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.5 to about 1:8.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.6 to about 1:8.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.7 to about 1:8.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.8 to about 1:8.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2.9 to about 1:8.2.

[0374] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3 to about 1:8.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.1 to about 1:8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.2 to about 1:7.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.3 to about 1:7.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.4 to about 1:7.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.5 to about 1:7.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.6 to about 1:7.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.7 to about 1:7.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.8 to about 1:7.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3.9 to about 1:7.2.

[0375] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4 to about 1:7.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.1 to about 1:7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.2 to about 1:6.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.3 to about 1:6.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.4 to about 1:6.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.5 to about1:6.6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.6 to about 1:6.5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.7 to about 1:6.4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.8 to about 1:6.3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4.9 to about 1:6.2.

[0376] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5 to about 1:6.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.1 to about 1:6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.2 to about 1:5.9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.3 to about 1:5.8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.4 to about 1:5.7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5.5 to about 1:5.6.

[0377] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>2. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>10. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>11. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1 >12. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>13. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>14. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>15. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>16. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>17. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>18. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:>19. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about l:>20.

[0378] In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 1.1. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:2. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:3. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:4. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:5. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:6. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:7. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:8. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:9. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:10. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 11. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1: 12. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:13. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:14. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 15. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:16. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 17. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1: 18. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:19. In some aspects, the weight ratio of (i) Racemic-THP to (ii) Racemic-BTC administered is about 1:20.

[0379] In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:4 to about 1:40. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:5 to about 1:39. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:6 to about 1:38. In some aspects, the weight ratioof (i) (?)-THP to (ii) Racemic-BTC administered is about 1:7 to about 1:37. In some aspects, the weight ratio of (i) (?)-THP to (ii) Racemic-BTC administered is about 1:8 to about 1:36. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:9 to about 1:35. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 10 to about 1:34. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:11 to about 1:33. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:12 to about 1:32. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:13 to about 1:31. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 14 to about 1:30. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:15 to about 1:29. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:16 to about 1:28. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:17 to about 1:27. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 18 to about 1:26. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:19 to about 1:25. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:20 to about 1:24. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:21 to about 1:23.

[0380] In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:4. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:5. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:6. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:7. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:8. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:9. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:10. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 11. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 12. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:13. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:14. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:15. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 16. In someaspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:17. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1: 18. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:19. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:20. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:21. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:22. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:23. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:24. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:25. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:26. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:27. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:28. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:29. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:30. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:31. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:32. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:33. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:34. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:35. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:36. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:37. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:38. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:39. In some aspects, the weight ratio of (i) (R)-THP to (ii) Racemic-BTC administered is about 1:40.

[0381] In some aspects, the weight ratio of (i) (R)-THP to (ii) (5)-BTC administered is about 1:2 to about 1:20. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:3 to about 1: 19. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:4 to about 1:18. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:5 to about 1:17. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:6 to about 1:16. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:7 to about 1: 15. Insome aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:8 to about 1:14. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:9 to about 1: 13. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 10 to about 1: 12.

[0382] In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:2. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:3. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:4. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:5. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:6. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:7. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:8. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:9. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 10. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 11. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 12. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:13. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 14. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:15. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 16. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 17. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:18. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1: 19. In some aspects, the weight ratio of (i) (R)-THP to (ii) (S)-BTC administered is about 1:20.

[0383] In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:1 to about 1:40. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:2 to about 1:39. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:3 to about 1:38. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:4 to about 1:37. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) amuscarinic acetylcholine receptor activator administered is about 1:5 to about 1:36. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:6 to about 1:35. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:7 to about 1:34. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:8 to about 1:33. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:9 to about 1:32. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:10 to about 1:31. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:11 to about 1:30. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:12 to about 1:29. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:13 to about 1:28. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:14 to about 1:27. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:15 to about 1:26. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:16 to about 1:25. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:17 to about 1:24. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:18 to about 1:23. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:19 to about 1:22. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:20 to about 1:21. In some aspects, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and ethopropazine or a pharmaceutically acceptable salt thereof.

[0384] In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:2 to about 1:8. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:3 to about 1:7. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:4 to about 1:6. In some aspects, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and ethopropazine or a pharmaceutically acceptable salt thereof.

[0385] In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:1.1. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:2. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:3. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:4. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:5. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:6. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:7. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:8. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:9. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1: 10. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1: 11. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:12. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1: 13. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activatoradministered is about 1:14. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1: 15. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:16. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1: 17. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:18. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:19. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:20. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:21. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:22. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:23. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:24. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:25. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:26. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:27. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:28. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:29. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:30. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:31. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:32. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptoractivator administered is about 1:33. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:34. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:35. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:36. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:37. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:38. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:39. In some aspects, the weight ratio of (i) a muscarinic acetylcholine receptor inhibitor to (ii) a muscarinic acetylcholine receptor activator administered is about 1:40. In some aspects, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and ethopropazine or a pharmaceutically acceptable salt thereof.Characterizing the Therapeutic Effect

[0386] In some aspects, the therapeutic effect and / or efficacy of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator is determined by measuring the serum concentration and / or the plasma concentration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

[0387] In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:20 ng / mL to about 1:40 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:21 ng / mL to about 1:39 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:22 ng / mL to about 1:38 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:23 ng / mL to about 1:37 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:24 ng / mL to about 1:36 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:25 ng / mL to about 1:35 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:26 ng / mL to about 1:34 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:27ng / mL to about 1:33 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:28 ng / mL to about 1:32 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:29 ng / mL to about 1:31 ng / mL after administration.

[0388] In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.1 ng / mL to about 1:3 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.2 ng / mL to about 1:2.9 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.3 ng / mL to about 1:2.8 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.4 ng / mL to about 1:2.7 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.5 ng / mL to about 1:2.6 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.6 ng / mL to about 1:2.5 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.7 ng / mL to about 1:2.4 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.8 ng / mL to about 1:2.3 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:1.9 ng / mL to about 1:2.2 ng / mL after administration.

[0389] In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:20 ng / mL to about 1:40 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:21 ng / mL to about 1:39 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:22 ng / mL to about 1:38 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:23 ng / mL to about 1:37 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:24 ng / mL to about 1:36 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:25 ng / mL to about 1:35 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:26 ng / mL to about 1:34 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:27 ng / mL to about 1:33 ng / mL after administration. Insome aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:28 ng / mL to about 1:32 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:29 ng / mL to about 1:31 ng / mL after administration.

[0390] In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.1 ng / mL to about 1:3 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.2 ng / mL to about 1:2.9 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.3 ng / mL to about 1:2.8 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.4 ng / mL to about 1:2.7 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.5 ng / mL to about 1:2.6 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.6 ng / mL to about 1:2.5 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.7 ng / mL to about 1:2.4 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.8 ng / mL to about 1:2.3 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) Racemic-BTC is about 1:1.9 ng / mL to about 1:2.2 ng / mL after administration.

[0391] In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (S)-BTC is about 1:20 ng / mL to about 1:40 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:21 ng / mL to about 1:39 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (5)-BTC is about 1:22 ng / mL to about 1:38 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (A')-BTC is about 1:23 ng / mL to about 1:37 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:24 ng / mL to about 1:36 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC about 1:25 ng / mL to about 1:35 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:26 ng / mL to about 1:34 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:27 ng / mL to about 1:33 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:28 ng / mL to about 1:32 ng / mL after administration. In someaspects, the serum concentration ratio of (i) (R)-THP to (ii) (5)-BTC is about 1:29 ng / mL to about 1:31 ng / mL after administration.

[0392] In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (5)-BTC is about 1:1.1 ng / mL to about 1:3 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:1.2 ng / mL to about 1:2.9 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (5)-BTC is about 1:1.3 ng / mL to about 1:2.8 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (S)-BTC is about 1:1.4 ng / mL to about 1:2.7 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (S)-BTC is about 1:1.5 ng / mL to about 1:2.6 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:1.6 ng / mL to about 1:2.5 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (A')-BTC is about 1:1.7 ng / mL to about 1:2.4 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) (S)-BTC is about 1:1.8 ng / mL to about 1:2.3 ng / mL after administration. In some aspects, the serum concentration ratio of (i) (R)-THP to (ii) fS')-BTC is about 1:1.9 ng / mL to about 1:2.2 ng / mL after administration.

[0393] In some aspects, the serum concentration ratio determined about 30 minutes to about 24 hours after the administration. In some aspects, the serum concentration ratio determined about 1 hour to about 22 hours after the administration. In some aspects, the serum concentration ratio determined about 2 hours to about 20 hours after the administration. In some aspects, the serum concentration ratio determined about 3 hours to about 17 hours after the administration. In some aspects, the serum concentration ratio determined about 4 hours to about 15 hours after the administration. In some aspects, the serum concentration ratio determined about 5 hours to about 12 hours after the administration. In some aspects, the serum concentration ratio determined about 6 hours to about 10 hours after the administration. In some aspects, the serum concentration ratio determined about 7 hours to about 9 hours after the administration. In some aspects, the serum concentration ratio determined about 30 minutes after the administration. In some aspects, the serum concentration ratio determined about 1 hour after the administration. In some aspects, the serum concentration ratio determined about 2 hours after the administration. In some aspects, the serum concentration ratio determined about 3 hours after the administration. In some aspects, the serum concentration ratio determined about 4 hours after the administration. In some aspects, the serum concentration ratio determined about 5 hours after theadministration. In some aspects, the serum concentration ratio determined about 6 hours after the administration. In some aspects, the serum concentration ratio determined about 7 hours after the administration. In some aspects, the serum concentration ratio determined about 8 hours after the administration. In some aspects, the serum concentration ratio determined about 9 hours after the administration. In some aspects, the serum concentration ratio determined about 10 hours after the administration. In some aspects, the serum concentration ratio determined about 11 hours after the administration. In some aspects, the serum concentration ratio determined about 12 hours after the administration. In some aspects, the serum concentration ratio determined about 13 hours after the administration. In some aspects, the serum concentration ratio determined about 14 hours after the administration. In some aspects, the serum concentration ratio determined about 15 hours after the administration. In some aspects, the serum concentration ratio determined about 16 hours after the administration. In some aspects, the serum concentration ratio determined about 17 hours after the administration. In some aspects, the serum concentration ratio determined about 18 hours after the administration. In some aspects, the serum concentration ratio determined about 19 hours after the administration. In some aspects, the serum concentration ratio determined about 20 hours after the administration. In some aspects, the serum concentration ratio determined about 21 hours after the administration. In some aspects, the serum concentration ratio determined about 22 hours after the administration. In some aspects, the serum concentration ratio determined about 23 hours after the administration. In some aspects, the serum concentration ratio determined about 24 hours after the administration.

[0394] In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:20 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:21 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:22 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:23 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:24 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:25 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:26 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii)Racemic-BTC is about 1:27 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:28 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:29 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:30 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:31 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:32 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:33 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:34 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:35 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC is about 1:36 ng / mL after administration. In some aspects, the serum concentration ratio of (i) Racemic-THP to (ii) Racemic-BTC ...

Claims

Claims:

1. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

2. The method of claim 1, wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fasted state.

3. The method of claim 1 or 2, wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered to a patient in a fed state.

4. The method of any one of claims 1-3, wherein the muscarinic acetylcholine receptor inhibitor distributes to the central nervous system and the peripheral nervous system in the patient.

5. The method of any one of claims 1-4, wherein the muscarinic acetylcholine receptor activator distributes predominately to the peripheral nervous system in the patient.

6. The method of any one of claims 1-5, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

7. The method of any one of claims 1-6, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

8. The method of any one of claims 1-7, wherein the muscarinic acetylcholine receptor inhibitor is provided in a sustained release dosage form.

9. The method of claim 8, wherein the sustained release dosage form comprises (R)- trihexyphenidyl or a pharmaceutically acceptable salt thereof.

10. The method of any one of claims 1-9, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

11. The method of any one of claims 1-10, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 98% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

12. The method of any one of claims 1-11, wherein the trihexyphenidyl having a stereochemical purity of at least 95% enantiomeric excess, or a pharmaceutically acceptable salt thereof is provided in a sustained release dosage form.

13. The method of any one of claims 1-12, wherein the muscarinic acetylcholine receptor activator is administered to the patient in an amount effective to reduce side effects of the muscarinic acetylcholine receptor inhibitor.

14. The method of any one of claims 1-13, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

15. The method of any one of claims 14, wherein the bethanechol or a pharmaceutically acceptable salt thereof is provided in a sustained release dosage form.

16. The method of any one of claims 14, wherein the bethanechol or a pharmaceutically acceptable salt thereof is provided in an immediate release version.

17. The method of any one of claims 1-16, wherein the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof.

18. The method of any one of claims 1-17, wherein the muscarinic acetylcholine receptor activator is (S)-bethanechol having a stereochemical purity of at least 95% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

19. The method of any one of claims 1-16, and 18, wherein the muscarinic acetylcholine receptor activator is (S)-bethanechol having a stereochemical purity of at least 98% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

20. The method of any one of claims 1-19, wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered simultaneously to the patient.

21. The method of any one of claims 1-20, wherein the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are each present in a single pharmaceutical composition that is administered to the patient.

22. The method of claim 21, wherein the pharmaceutical composition is in the form of a tablet, troche, liquid, drop, capsule, caplet, gel cap, sublingual formulation, bilayer tablet, microparticulate, or spray.

23. The method of claim 21 or 22, wherein the pharmaceutical composition is in the form of a bilayer tablet.

24. The method of claim 21 or 22, wherein the pharmaceutical composition is in the form of a microparticulate.

25. The method of any one of claims 20-24, wherein the pharmaceutical composition comprises (i) a controlled release component containing the muscarinic acetylcholine receptor inhibitor and (ii) an immediate release component containing the muscarinic acetylcholine receptor activator.

26. The method of any one of claims 20-25, wherein the pharmaceutical composition is administered orally to the patient.

27. The method of claim 20-26, wherein the pharmaceutical composition is administered daily.

28. The method of claim 20-26, wherein the pharmaceutical composition is administered twice per day.

29. The method of claim 20-26, wherein the pharmaceutical composition is administered three times per day.

30. The method of any one of claims 1-29, wherein the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage that, in the absence of a muscarinic acetylcholine receptor activator, causes at least one adverse side effect selected from dry mouth, dry eye, blurry vision, tachycardia, confusion, forgetfulness, hallucination, constipation, urine retention, and brain fog.

31. The method of any one of claims 1-30, where the muscarinic acetylcholine receptor inhibitor is orally administered at an initial dosage of greater than 10 mg / day.

32. The method of any one of claims 1-31, wherein the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage in the range of from about 10 mg to about 20 mg.

33. The method of any one of claims 1-28, wherein the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 15 mg.

34. The method of any one of claims 1-29, wherein the muscarinic acetylcholine receptor activator is orally administered at a dosage in the range of from about 60 mg to about 120 mg.

35. The method of any one of claims 1-34, wherein the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 90 mg.

36. The method of any one of claims 1-34, wherein the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 75 mg.

37. The method of any one of claims 1-34 and 36, wherein the muscarinic acetylcholine receptor inhibitor is orally administered at a dosage of about 15 mg, and wherein the muscarinic acetylcholine receptor activator is orally administered at a dosage of about 75 mg.

38. The method of any one of claims 1-37, wherein the movement disorder is dystonia.

39. The method of any one of claims 1-37, wherein the movement disorder is primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, or cerebral palsy-associated dystonia.

40. The method of any one of claims 1-37, wherein the movement disorder is focal dystonia.

41. The method of claim 40, wherein the focal dystonia is cervical dystonia, blepharospasm, hand dystonia, writer’s cramp, musician’s dystonia, leg dystonia, or foot dystonia.

42. The method of any one of claims 1-37, wherein the movement disorder is segmental dystonia, hemidystonia, multifocal dystonia, or generalized dystonia.

43. The method of any one of claims 1-37, wherein the movement disorder is idiopathic in origin.

44. The method of any of claims 1-37, wherein the movement disorder is a geneticdystonia.

45. The method of claim 44, where the genetic dystonia is associated with a mutation in one or more genes selected from TORI A, THAP1, AN03, GNAL, KMT2B, GCH1, SPR, TAF1, PRKRA, ATP1A3, SGCE, PNKD, PRRT2, SLC2A1, and ECHS1.

46. The method of any one of claims 1-37, wherein the movement disorder is Multiple System Atrophy, Progressive Supranuclear Palsy, or tremor.

47. The method of any one of claims 1-37, wherein the movement disorder is Parkinson’s disease, drug-induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies.

48. The method of any one of claims 1-37, wherein the movement disorder is Parkinson’s disease.

49. The method of any one of claims 1-37, wherein the movement disorder is tremor in Parkinson’s disease.

50. The method of any one of claims 1-49, wherein the patient experiences fewer than four occurrences of dizziness per week while receiving the muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

51. The method of any one of claims 1-50, wherein the patient experiences fewer than four occurrences of lightheadedness per week while receiving the muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

52. The method of any one of claims 1-51, wherein the patient experiences fewer than three occurrences of headache per week while receiving the muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

53. The method of any one of claims 1-52, wherein the patient experiences fewer than three occurrences of nausea per week while receiving the muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

54. The method of any one of claims 1-53, wherein the patient experiences fewer than five occurrences per week of an adverse side effect selected from vomiting, diarrhea, salivation, and anorexia.

55. The method of any one of claims 1-54, wherein the patient is an adult human.

56. The method of any one of claims 1-54, wherein the patient is a pediatric human.

57. The method of any one of claims 1-55, wherein the patient is an adult human about 65 years or older.

58. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is a human patient aged 65 years or older.

59. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 10-20 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70-80 mg.

60. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 15 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 75 mg.

61. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 15 mg, and the muscarinic acetylcholinereceptor activator is administered to the patient at a dose of about 75 mg, wherein the a muscarinic acetylcholine receptor inhibitor is (R)-THP or a pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is BTC or a pharmaceutically acceptable salt thereof.

62. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fasted state.

63. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fasted state, and wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 15 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 75 mg, wherein the a muscarinic acetylcholine receptor inhibitor is (R)-THP or a pharmaceutically acceptable salt thereof, and wherein the muscarinic acetylcholine receptor activator is BTC or a pharmaceutically acceptable salt thereof.

64. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fed state.

65. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at leastone side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fed or fasted state.

66. A method of treating a movement disorder in a patient comprising:administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(minimum) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

67. A method of treating a movement disorder in a patient comprising:administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the plasma C(trough) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

68. An oral pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat a movement disorder and (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier,wherein the composition is sufficient to provide an in vivo plasma profile of the muscarinic acetylcholine receptor inhibitor when administered to a subject in need thereof, andwherein the plasma C(minimum) of muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml.

69. An oral pharmaceutical composition, comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat a movement disorder and (ii) amuscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier,wherein the composition is sufficient to provide an in vivo plasma profile of the acetylcholine receptor inhibitor when administered to a patient in need thereof, and wherein the plasma C(trough) of muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml.

70. The oral pharmaceutical composition of claim 68 or 69, wherein the rate of rise of the plasma concentration of the muscarinic acetylcholine receptor inhibitor is less than about 10 ng / mL / hr.

71. The oral pharmaceutical composition of any one of claims 68-70, wherein the oral pharmaceutical composition is a controlled release formulation.

72. The oral pharmaceutical composition of any one of claims 68-71, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

73. The oral pharmaceutical composition of claim 72, wherein the trihexyphenidyl or pharmaceutically acceptable salt thereof is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

74. The oral pharmaceutical composition of claim 73, wherein the (R)-trihexyphenidyl or pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomeric excess.

75. The oral pharmaceutical composition of any one of claims 68-74, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

76. The oral pharmaceutical composition of any one of claims 68-75, wherein the magnitude or severity of at least one side effect of the muscarinic acetylcholine receptor inhibitor is reduced in the subject compared to a subject administered an immediate release formulation of the muscarinic acetylcholine receptor inhibitor alone.

77. The oral pharmaceutical composition of any one of claims 68-76, wherein the oral pharmaceutical composition is dosed once per day.

78. The oral pharmaceutical composition of any one of claims 68-77 wherein the oral pharmaceutical composition is dosed twice per day.

79. The oral pharmaceutical composition of any one of claims 68-78, wherein the oral pharmaceutical composition is in the form of a bilayer tablet.

80. The oral pharmaceutical composition of any one of claims 68-78, wherein the oral pharmaceutical composition is in the form of a microparticulate.

81. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, and wherein an efficacious dose of the muscarinic acetylcholine receptor inhibitor is reached within 30 days after administration of the muscarinic acetylcholine receptor inhibitor.

82. The method of claim 81, wherein the efficacious dose is reached twenty-eight days after administration of the muscarinic acetylcholine receptor inhibitor.

83. The method of claim 81, wherein the efficacious dose is reached twenty -two days after administration of the muscarinic acetylcholine receptor inhibitor.

84. The method of claim 81, wherein the efficacious dose is reached twenty-one days after administration of the muscarinic acetylcholine receptor inhibitor.

85. The method of claim 81, wherein the efficacious dose is reached fourteen days after administration of the muscarinic acetylcholine receptor inhibitor.

86. The method of claim 81, wherein the efficacious dose is reached seven days after administration of the muscarinic acetylcholine receptor inhibitor.

87. The method of claim 81, wherein the efficacious dose is reached five days after administration of the muscarinic acetylcholine receptor inhibitor.

88. The method of claim 81, wherein the efficacious dose is reached one day after administration of the muscarinic acetylcholine receptor inhibitor.

89. The method of any one of claims 81-88, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP or a pharmaceutically acceptable salt thereof.

90. The method of claim 89, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg.

91. The method of claim 89 or 90, wherein the (R)-THP is sustained release (R)-THP.

92. The method of any one of claims 89-91, wherein the muscarinic acetylcholine receptor activator is BTC or a pharmaceutically acceptable salt thereof.

93. The method of claim 92, wherein BTC or pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

94. The method of claim 92 or 93, wherein the BTC is sustained release BTC.

95. The method of any one of claims 89-94, wherein the muscarinic acetylcholine receptor inhibitor is (R)-THP or a pharmaceutically acceptable salt thereof, wherein the muscarinic acetylcholine receptor activator is BTC or a pharmaceutically acceptable salt thereof, and wherein the efficacious dose is reached 22 days after administration of the (R)-THP.

96. A pharmaceutical composition comprising:a. about 2.8% by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 44% by weight dicalcium phosphate anhydrous;f. about 2.2% by weight lactose; andg. about 1% by weight magnesium stearate.

97. A pharmaceutical composition comprising:a. about 5.60 mg (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 4.4 mg lactose; andg. about 2 mg magnesium stearate.

98. A pharmaceutical composition comprising:a. about 2.8% by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 30% by weight hydroxpropyl methylcellulose 100SR;c. about 10% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 44% by weight dicalcium phosphate anhydrous;f. about 2.2% by weight lactose; andg. about 1% by weight magnesium stearate.

99. A pharmaceutical composition comprising:a. about 5.60 mg (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 60 mg hydroxpropyl methylcellulose 100SR;c. about 20 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 4.4 mg lactose; andg. about 2 mg magnesium stearate.

100. A pharmaceutical composition comprising:a. about 5.6% by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 30% by weight hydroxpropyl methylcellulose 100SR;c. about 10% by weight microcrystalline cellulose;d. about 53.4% by weight lactose; ande. about 1% by weight magnesium stearate.

101. A pharmaceutical composition comprising:a. about 5.60 mg (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 30 mg hydroxpropyl methylcellulose 100SR;c. about 10 mg microcrystalline cellulose;d. about 53.4 mg lactose; ande. about 1 mg magnesium stearate.

102. A pharmaceutical composition comprising:a. about 15.25% by weight bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 20% by weight microcrystalline cellulose;e. about 23.75% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

103. A pharmaceutical composition comprising:a. about 30.5 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 40 mg microcrystalline cellulose;e. about 47.5 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

104. A pharmaceutical composition comprising:a. about 1-5% by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 40-50% by weight dicalcium phosphate anhydrous;f. about 1-5% by weight lactose; andg. about 0.1-3% by weight magnesium stearate.

105. A pharmaceutical composition comprising:a. about 1-10 mg (R)-trihexy phenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 83-93 mg dicalcium phosphate anhydrous;f. about 1-10 mg lactose; andg. about 0.5-5 mg magnesium stearate.

106. A pharmaceutical composition comprising:a. about 1-5% by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 25-35% by weight hydroxpropyl methylcellulose 100SR;c. about 5-15% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 40-50% by weight dicalcium phosphate anhydrous;f. about 1-5% by weight lactose; andg. about 0.1-3% by weight magnesium stearate.

107. A pharmaceutical composition comprising:a. about 1-10 mg (R)-trihexy phenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 55-65 mg hydroxpropyl methylcellulose 100SR;c. about 15-25 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 83-93 mg dicalcium phosphate anhydrous;f. about 1-10 mg lactose; andg. about 0.1-3 mg magnesium stearate.

108. A pharmaceutical composition comprising:a. about 1-10% by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 25-35% by weight hydroxpropyl methylcellulose 100SR;c. about 5-15% by weight microcrystalline cellulose;d. about 47-57% by weight lactose; ande. about 0.1-3% by weight magnesium stearate.

109. A pharmaceutical composition comprising:a. about 1-10 mg (R)-trihexy phenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 25-35 mg hydroxpropyl methylcellulose 100SR;c. about 5-15 mg microcrystalline cellulose;d. about 47-57 mg lactose; ande. about 0.1-3 mg magnesium stearate.

110. A pharmaceutical composition comprising:a. about 1.4 % by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 44% by weight dicalcium phosphate anhydrous;f. about 3.6% by weight lactose; andg. about 1% by weight magnesium stearate.

111. A pharmaceutical composition comprising:a. about 2.8 mg (R)-trihexy phenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 7.2 mg lactose; andg. about 1 mg magnesium stearate.

112. A pharmaceutical composition comprising:a. about 0.1-3 % by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 39-49% by weight dicalcium phosphate anhydrous;f. about 1-8% by weight lactose; andg. about 0.1-3% by weight magnesium stearate.

113. A pharmaceutical composition comprising:a. about 0.1-5 mg (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 83-93 mg dicalcium phosphate anhydrous;f. about 2-12 mg lactose; andg. about 0.1-3 mg magnesium stearate.

114. A pharmaceutical composition comprising:a. about 11.2 mg (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 86.8 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

115. A pharmaceutical composition comprising:a. about 5.6 % by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 43.4% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

116. A pharmaceutical composition comprising:a. about 6-16 mg (R)-trihexy phenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 81-91 mg dicalcium phosphate anhydrous; andf. about 0.1-5 mg magnesium stearate.

117. A pharmaceutical composition comprising:a. about 0.1-10 % by weight (R)-trihexyphenidyl (R-THP) or a pharmaceutically acceptable salt thereof;b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 38-48% by weight dicalcium phosphate anhydrous; andf. about 0.1-3% by weight magnesium stearate.

118. A pharmaceutical composition comprising:a. about 10-20% by weight bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 15-25% by weight microcrystalline cellulose;e. about 18-28% by weight dicalcium phosphate anhydrous; andf. about 0.1-3% by weight magnesium stearate.

119. A pharmaceutical composition comprising:a. about 25-35 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 35-45 mg microcrystalline cellulose;e. about 43-53 mg dicalcium phosphate anhydrous; andf. about 0.1-3 mg magnesium stearate.

120. A pharmaceutical composition comprising:a. about 30.5 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 40 mg microcrystalline cellulose;e. about 47.5 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

121. A pharmaceutical composition comprising:a. about 15.25% by weight bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 20% by weight microcrystalline cellulose;e. about 23.75% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

122. A pharmaceutical composition comprising:a. about 61.5 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 37 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

123. A pharmaceutical composition comprising:a. about 30.5% by weight bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 18.5% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

124. A pharmaceutical composition comprising:a. about 122 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 40 mg hydroxpropyl methylcellulose 100SR;c. about 120 mg hydroxpropyl methylcellulose 15,000SR;d. about 40 mg microcrystalline cellulose;e. about 74 mg dicalcium phosphate anhydrous; andf. about 4 mg magnesium stearate.

125. A pharmaceutical composition comprising:a. about 56-66 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 32-42 mg dicalcium phosphate anhydrous; andf. about 0.1-3 mg magnesium stearate.

126. A pharmaceutical composition comprising:a. about 25-35% by weight bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 13-23% by weight dicalcium phosphate anhydrous; andf. about 0.1-3% by weight magnesium stearate.

127. A pharmaceutical composition comprising:a. about 117-127 mg bethanechol (BTC) or a pharmaceutically acceptable salt thereof;b. about 35-45 mg hydroxpropyl methylcellulose 100SR;c. about 115-125 mg hydroxpropyl methylcellulose 15,000SR;d. about 35-45 mg microcrystalline cellulose;e. about 69-79 mg dicalcium phosphate anhydrous; andf. about 1-8 mg magnesium stearate.

128. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof; b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 4.4 mg lactose;g. about 2 mg magnesium stearate;wherein the sustained release BTC component comprises:a. about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 40 mg microcrystalline cellulose;e. about 47.5 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

129. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof;b. about 60 mg hydroxpropyl methylcellulose 100SR;c. about 20 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 4.4 mg lactose; andg. about 2 mg magnesium stearate;wherein the sustained release BTC component comprises:a. about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 40 mg microcrystalline cellulose;e. about 47.5 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

130. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 5.60 mg R-THP or a pharmaceutically acceptable salt thereof; b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 4.4 mg lactose; andg. about 2 mg magnesium stearate;wherein the sustained release BTC component comprises:a. about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 40 mg microcrystalline cellulose;e. about 47.5 mg dicalcium phosphate anhydrous; andf. about 2 mg magnesium stearate.

131. A pharmaceutical composition comprising a sustained (R)-trihexyphenidyl (R-THP) component and a sustained release bethanechol (BTC) component,wherein the sustained release R-THP component comprises:a. about 2.8 mg R-THP or a pharmaceutically acceptable salt thereof; b. about 20 mg hydroxpropyl methylcellulose 100SR;c. about 60 mg hydroxpropyl methylcellulose 15,000SR;d. about 20 mg microcrystalline cellulose;e. about 88 mg dicalcium phosphate anhydrous;f. about 7.2 mg lactose;g. about 1 mg magnesium stearate;wherein the sustained release BTC component comprises:g. about 30.5 mg BTC or a pharmaceutically acceptable salt thereof; h. about 20 mg hydroxpropyl methylcellulose 100SR;i. about 60 mg hydroxpropyl methylcellulose 15,000SR;j. about 40 mg microcrystalline cellulose;k. about 47.5 mg dicalcium phosphate anhydrous; andl. about 2 mg magnesium stearate.

132. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 44% by weight dicalcium phosphate anhydrous;f. about 2.2% by weight lactose; andg. about 1% by weight magnesium stearate;wherein the sustained release BTC component comprises:a. about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 20% by weight microcrystalline cellulose;e. about 23.75% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

133. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 30% by weight hydroxpropyl methylcellulose 100SR;c. about 10% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 44% by weight dicalcium phosphate anhydrous;f. about 2.2% by weight lactose; andg. about 1% by weight magnesium stearate;wherein the sustained release BTC component comprises:a. about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 20% by weight microcrystalline cellulose;e. about 23.75% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

134. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 5.6% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 30% by weight hydroxpropyl methylcellulose 100SR;c. about 10% by weight microcrystalline cellulose;d. about 53.4% by weight lactose; ande. about 1% by weight magnesium stearate;wherein the sustained release BTC component comprises:g. about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; h. about 10% by weight hydroxpropyl methylcellulose 100SR;i. about 30% by weight hydroxpropyl methylcellulose 15,000SR;j. about 20% by weight microcrystalline cellulose;k. about 23.75% by weight dicalcium phosphate anhydrous; andl. about 1% by weight magnesium stearate.

135. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:h. about 1.4% by weight R-THP or a pharmaceutically acceptable salt thereof; i. about 10% by weight hydroxpropyl methylcellulose 100SR;j. about 30% by weight hydroxpropyl methylcellulose 15,000SR;k. about 10% by weight microcrystalline cellulose;l. about 44% by weight dicalcium phosphate anhydrous;m. about 3.6% by weight lactose; andn. about 1% by weight magnesium stearate;wherein the sustained release BTC component comprises:g. about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof; h. about 10% by weight hydroxpropyl methylcellulose 100SR;i. about 30% by weight hydroxpropyl methylcellulose 15,000SR;j. about 20% by weight microcrystalline cellulose;k. about 23.75% by weight dicalcium phosphate anhydrous; andl. about 1% by weight magnesium stearate.

136. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 40-50% by weight dicalcium phosphate anhydrous;f. about 1-5% by weight lactose; andg. about 0.1-3% by weight magnesium stearate;wherein the sustained release BTC component comprises:a. about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof; b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 15-25% by weight microcrystalline cellulose;e. about 18-28% by weight dicalcium phosphate anhydrous; andf. about 0.1-3% by weight magnesium stearate.

137. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 25-35% by weight hydroxpropyl methylcellulose 100SR;c. about 5-15% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 40-50% by weight dicalcium phosphate anhydrous;f. about 1-5% by weight lactose; andg. about 0.1-3% by weight magnesium stearate;wherein the sustained release BTC component comprises:a. about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof; b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR;d. about 15-25% by weight microcrystalline cellulose;e. about 18-28% by weight dicalcium phosphate anhydrous; andf. about 0.1-3% by weight magnesium stearate.

138. A pharmaceutical composition comprising a sustained (R)-trihexyphenidyl (R-THP) component and a sustained release bethanechol (BTC) component,wherein the sustained release R-THP component comprises:a. about 1-5% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 5-15% by weight microcrystalline cellulose;e. about 40-50% by weight dicalcium phosphate anhydrous;f. about 1-5% by weight lactose; andg. about 0.1-3% by weight magnesium stearate;wherein the sustained release BTC component comprises:a. about 10-20% by weight BTC or a pharmaceutically acceptable salt thereof; b. about 5-15% by weight hydroxpropyl methylcellulose 100SR;c. about 25-35% by weight hydroxpropyl methylcellulose 15,000SR; d. about 15-25% by weight microcrystalline cellulose;e. about 18-28% by weight dicalcium phosphate anhydrous; andf. about 0.1-3% by weight magnesium stearate.

139. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof; b. about 25-35 mg hydroxpropyl methylcellulose 100SR;c. about 5-15 mg microcrystalline cellulose;d. about 47-57 mg lactose; ande. about 0.1-3 mg magnesium stearate;wherein the sustained release BTC component comprises:a. about 25-35 mg BTC or a pharmaceutically acceptable salt thereof; b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 35-45 mg microcrystalline cellulose;e. about 43-53 mg dicalcium phosphate anhydrous; andf. about 0.1-3 mg magnesium stearate.

140. A pharmaceutical composition comprising a sustained release (R)-trihexyphenidyl (R- THP) component and a sustained release bethanechol (BTC) component, wherein the sustained release R-THP component comprises:a. about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof; b. about 55-65 mg hydroxpropyl methylcellulose 100SR;c. about 15-25 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 83-93 mg dicalcium phosphate anhydrous;f. about 1-10 mg lactose; andf. about 0.1-3 mg magnesium stearate;wherein the sustained release BTC component comprises:a. about 25-35 mg BTC or a pharmaceutically acceptable salt thereof; b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 35-45 mg microcrystalline cellulose;e. about 43-53 mg dicalcium phosphate anhydrous; andf. about 0.1-3 mg magnesium stearate.

141. A pharmaceutical composition comprising a sustained (R)-trihexyphenidyl (R-THP) component and a sustained release bethanechol (BTC) component,wherein the sustained release R-THP component comprises:a. about 1-10 mg R-THP or a pharmaceutically acceptable salt thereof; b. about 15-25 mg hydroxpropyl methylcellulose 100SR;c. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;d. about 15-25 mg microcrystalline cellulose;e. about 83-93 mg dicalcium phosphate anhydrous;f. about 1-10 mg lactose; andg. about 0.5-5 mg magnesium stearate;wherein the sustained release BTC component comprises:g. about 25-35 mg BTC or a pharmaceutically acceptable salt thereof; h. about 15-25 mg hydroxpropyl methylcellulose 100SR;i. about 55-65 mg hydroxpropyl methylcellulose 15,000SR;j. about 35-45 mg microcrystalline cellulose;k. about 43-53 mg dicalcium phosphate anhydrous; andl. about 0.1-3 mg magnesium stearate.

142. The pharmaceutical composition of any one of claims 96-101 and 104-118, wherein the pharmaceutical composition provides a R-THP plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

143. The pharmaceutical composition of any one of claims 128-141, wherein the pharmaceutical composition provides a C(max) plasma concentration of R-THP: BTC of about 1: 1 to about 1:20.

144. The pharmaceutical composition of any one of claims 128-141, wherein the pharmaceutical composition provides an area under the curve (AUC) plasma concentration of R-THP: BTC of about 1:1 to about 1:40.

145. The pharmaceutical composition of any one of claims 96-101 and 104-118, wherein the pharmaceutical composition provides a R-THP C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

146. The pharmaceutical composition of any one of claims 96-101 and 104-118, wherein the pharmaceutical composition provides a R-THP C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

147. The pharmaceutical composition of any one of claims 128-141, wherein the pharmaceutical composition provides a BTC: R-THP plasma concentration ratio of about 1.5:1 from between 0 to about 10 hours after administration of the pharmaceutical composition.

148. The pharmaceutical composition of any one of claims 128-151, wherein the pharmaceutical composition provides a BTC: R-THP plasma concentration ratio ofgreater than 1.5:1 from between 0 to about 10 hours after administration of the pharmaceutical composition.

149. The pharmaceutical composition of any one of claims 96-148 for use as a medicament.

150. The pharmaceutical composition of any one of claims 96-148 for use in the treatment of a movement disorder.

151. The pharmaceutical composition of claim 150, wherein the movement disorder is dystonia.

152. The pharmaceutical composition of claim 150, wherein the movement disorder is Parkinson’s disease.

153. The pharmaceutical composition of claim 150, wherein the movement disorder is tremor in Parkinson’s disease.

154. The pharmaceutical composition of any one of claims 96-153, wherein the pharmaceutical composition is in the form of a bilayer tablet.

155. The pharmaceutical composition of any one of claims 96-153, wherein the pharmaceutical composition is in the form of a microparticulate.

156. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1:1 to about 1:20.

157. The method of claim 156, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

158. The method of claim 157, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

159. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the composition demonstrates an area under the curve (AUC) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

160. The method of claim 159, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

161. The method of claim 160, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

162. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

163. The method of claim 162, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

164. The method of claim 163, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

165. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

166. The method of claim 165, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

167. The method of claim 166, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

168. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the muscarinic acetylcholine receptor inhibitor demonstrates a plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

169. The method of claim 168, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

170. The method of claim 169, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

171. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

172. The method of claim 171, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

173. The method of claim 172, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

174. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition demonstrates an area under the curve (AUC) plasma ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1:1 to about 1:40.

175. The method of claim 174, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

176. The method of claim 175, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

177. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(minimum) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

178. The method of claim 177, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

179. The method of claim 178, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

180. A method of treating a movement disorder in a patient, comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(trough) plasmaconcentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

181. The method of claim 180, wherein the muscarinic acetylcholine receptor inhibitor comprises (R)-THP or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator comprises BTC or a pharmaceutically acceptable salt thereof.

182. The method of claim 181, wherein the (R)-THP or pharmaceutically acceptable salt thereof is administered at a dose of 15 mg, and the BTC or a pharmaceutically acceptable salt thereof is administered at a dose of 75 mg.

183. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

184. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder.

185. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is a human patient aged 65 years or older.

186. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient inneed thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is a human patient aged 65 years or older.

187. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 10-20 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70-80 mg.

188. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the muscarinic acetylcholine receptor inhibitor is administered to the patient at a dose of about 10-20 mg, and the muscarinic acetylcholine receptor activator is administered to the patient at a dose of about 70-80 mg.

189. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fasted state.

190. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fasted state.

191. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fed state.

192. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the patient is in a fed state.

193. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising:administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(minimum) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

194. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising:administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein the plasma C(minimum) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

195. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising:administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the plasma C(trough) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

196. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising:administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the plasma C(trough) value of the muscarinic acetylcholine receptor inhibitor is about 20-30 ng / ml after administration of the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator.

197. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein an efficacious dose of the muscarinic acetylcholine receptor inhibitor is reached within 30 days after administration of the muscarinic acetylcholine receptor inhibitor.

198. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder, wherein an efficacious dose of the muscarinic acetylcholine receptor inhibitor is reached within 30 days after administration of the muscarinic acetylcholine receptor inhibitor.

199. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1:1 to about 1:20.

200. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinicacetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1:1 to about 1:20.

201. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the composition demonstrates an area under the curve (AUC) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

202. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the composition demonstrates an area under the curve (AUC) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:40.

203. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / ormagnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

204. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(minimum) plasma concentration of about 5 ng / ml to about 40 ng / ml.

205. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

206. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein the muscarinic acetylcholine receptor inhibitor demonstrates a C(trough) plasma concentration of about 5 ng / ml to about 40 ng / ml.

207. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the muscarinic acetylcholine receptor inhibitor demonstrates a plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

208. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the muscarinic acetylcholine receptor inhibitor demonstrates a plasma concentration rate of rise of about 1 ng / mL / hr to about 20 ng / mL / hr.

209. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

210. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition demonstrates a C(max) plasma concentration ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1: 1 to about 1:20.

211. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition demonstrates an area under the curve (AUC) plasma ratio of the muscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1:1 to about 1:40.

212. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition demonstrates an area under the curve (AUC) plasma ratio of themuscarinic acetylcholine receptor inhibitor to the muscarinic receptor activator of about 1:1 to about 1:40.

213. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(minimum) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

214. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(minimum) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

215. A muscarinic acetylcholine receptor inhibitor for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) the muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(trough) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

216. A muscarinic acetylcholine receptor activator for use in a method of treating a movement disorder in a patient, the method comprising administering to a patient in need thereof a composition comprising (i) a muscarinic acetylcholine receptor inhibitor in an amount effective to treat the movement disorder and (ii) the muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or magnitude of at least one side effect of the muscarinic acetylcholine receptor inhibitor, to thereby treat the movement disorder,wherein after administering the composition to the patient in a fasted state, the composition provides an in vivo plasma profile, and wherein the C(trough) plasma concentration of the muscarinic acetylcholine receptor inhibitor of about 5 ng / ml to about 40 ng / ml.

217. The pharmaceutical composition of claim 96, wherein the pharmaceutical composition is administered to a patient with a movement disorder selected from dystonia, primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-associated dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer’s cramp, musician’s dystonia, leg dystonia, foot dystonia, idiopathic in origin, a genetic dystonia, Multiple System Atrophy, Progressive Supranuclear Palsy, tremor, Parkinson’s disease, tremor in Parkinson’s disease, drug-induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies.

218. The pharmaceutical composition of claim 96, wherein the pharmaceutical composition is administered to a patient with dystonia.

219. The pharmaceutical composition of claim 96, wherein the pharmaceutical composition is administered to a patient with tremor in Parkinson’s disease.

220. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition is a bilayer tablet.

221. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition comprises the R-THP and the BTC in a weight ratio of R-THP to BTC of about 1:5.

222. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition provides a plasma C(minimum) concentration of the R-THP of greater than or equal to about 25 ng / ml after administration of the pharmaceutical composition.

223. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition provides a plasma concentration rate of rise of the R-THP is less than or equal to about 10 ng / ml / hr after administration of the pharmaceutical composition.

224. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition provides an area under the curve (AUC) plasma concentration of the R- THP is about 800 to about 1200 ng*hr / ml after administration of the pharmaceutical composition.

225. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition provides after administration of the pharmaceutical composition:a. a plasma C(minimum) concentration of the R-THP of greater than or equal to about 25 ng / ml;b. a plasma concentration rate of rise of the R-THP is less than or equal to about 10 ng / ml / hr; andc. an area under the curve (AUC) plasma concentration of the R-THP is about 800 to about 1200 ng*hr / ml.

226. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition is administered to a patient with a movement disorder selected from dystonia, primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-associated dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer’s cramp, musician’s dystonia, leg dystonia, foot dystonia, idiopathic in origin, a genetic dystonia, Multiple System Atrophy, Progressive Supranuclear Palsy, tremor, Parkinson’s disease, tremor in Parkinson’s disease, drug-induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies.

227. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition is administered to a patient with dystonia.

228. The pharmaceutical composition of claim 132, wherein the pharmaceutical composition is administered to a patient with tremor in Parkinson’s disease.

229. The pharmaceutical composition of claim 132, wherein the magnitude or severity of at least one side effect of the R-THP or a pharmaceutically acceptable salt thereof is reduced in the patient compared to a patient administered an immediate release formulation of trihexyphenidyl or a pharmaceutically acceptable salt thereof alone.

230. The pharmaceutical composition of claim 229, wherein the side effect is selected from the group consisting of dry mouth, dry eye, blurry vision, tachycardia, constipation, urine retention, impaired vision, constipation, nausea, cramping, reduced urinary voiding, flushed skin, fever, reduced sweating, cardiac arrhythmia, dizziness, lightheadedness, headache, drowsiness, confusion, reduced concentration, brain fog, euphoria, elevated mood, hallucinations, agitation, irritability, sensory disturbances, blurry vision, brain fog, and combinations thereof.

231. A method of treating a movement disorder in a patient in need thereof, comprising administering (R)-trihexyphenidyl (R-THP) and bethanechol (BTC),wherein the R-THP is provided as a sustained release pharmaceutical composition comprising:a. about 2.8% by weight R-THP or a pharmaceutically acceptable salt thereof; b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 10% by weight microcrystalline cellulose;e. about 44% by weight dicalcium phosphate anhydrous;f. about 2.2% by weight lactose; andg. about 1% by weight magnesium stearate; andwherein the BTC is provided as a sustained release pharmaceutical composition comprising:a. about 15.25% by weight BTC or a pharmaceutically acceptable salt thereof;b. about 10% by weight hydroxpropyl methylcellulose 100SR;c. about 30% by weight hydroxpropyl methylcellulose 15,000SR;d. about 20% by weight microcrystalline cellulose;e. about 23.75% by weight dicalcium phosphate anhydrous; andf. about 1% by weight magnesium stearate.

232. The method of claim 231, wherein the R-THP and the BTC are each present in a single pharmaceutical composition that is administered to the patient.

233. The method of claim 231, wherein the single pharmaceutical composition is a bilayer tablet.

234. The method of claim 231, wherein the R-THP and the BTC are administered in a weight ratio of R-THP to BTC of about 1:5.

235. The method of claim 231, wherein the movement disorder is selected from dystonia, primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-associated dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer’s cramp, musician’s dystonia, leg dystonia, foot dystonia, idiopathic in origin, a genetic dystonia, Multiple System Atrophy, Progressive Supranuclear Palsy, tremor, Parkinson’s disease, tremor in Parkinson’s disease, drug- induced Parkinsonism, Huntington’s disease, or dementia with Lewy Bodies.

236. The method of claim 231, wherein the movement disorder is dystonia.

237. The method of claim 231, wherein the movement disorder is tremor in Parkinson’s disease.

238. The method of claim 231, wherein the magnitude or severity of at least one side effect of the R-THP or a pharmaceutically acceptable salt thereof is reduced in the patient compared to a patient administered an immediate release formulation of trihexyphenidyl or a pharmaceutically acceptable salt thereof alone.

239. The method of claim 238, wherein the side effect is selected from the group consisting of dry mouth, dry eye, blurry vision, tachycardia, constipation, urine retention, impaired vision, constipation, nausea, cramping, reduced urinary voiding, flushed skin, fever, reduced sweating, cardiac arrhythmia, dizziness, lightheadedness, headache, drowsiness, confusion, reduced concentration, brain fog, euphoria, elevatedmood, hallucinations, agitation, irritability, sensory disturbances, blurry vision, brain fog, and combinations thereof.

240. The method of claim 231, wherein the plasma C(minimum) concentration of the R- THP is greater than or equal to about 25 ng / ml after the administration.

241. The method of claim 231, wherein the plasma concentration rate of rise of the R-THP is less than or equal to about 10 ng / ml / hr after the administration.

242. The method of claim 231, wherein the area under the curve (AUC) plasma concentration of the R-THP is about 800 to about 1200 ng*hr / ml after the administration.

243. The method of claim 231, wherein after the administration the R-THP in the patient has:a. a plasma C(minimum) concentration of greater than or equal to about 25 ng / ml;b. a plasma concentration rate of rise of less than or equal to about 10 ng / ml / hr;andc. an area under the curve (AUC) plasma concentration of about 800 to about 1200 ng*hr / ml.

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