Therapeutic methods and compositions for treating motor disorders

Abstract

The present 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.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority and interest under U.S. Provisional Application 63 / 464,409 filed May 5, 2023, and U.S. Provisional Application 63 / 615,960 filed December 29, 2023, each of which is incorporated herein by reference in whole.

[0002] Field of Invention The present invention relates to 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 technology]

[0003] background Motor disorders affect a significant number of patients. One such motor disorder, dystonia, is a neurological motor disorder characterized by involuntary (unintended) muscle contractions that cause slow, repetitive movements or postural abnormalities, which may be painful. This condition can affect a part of the body, including the torso (focal dystonia), two or more adjacent parts (segmental dystonia), or multiple parts of the body (generalized dystonia). Muscle spasms can range from mild to severe. Dystonia can be primary or secondary. Primary dystonia is when dystonia is the only neurological condition experienced by the individual. Secondary dystonia is when dystonia is caused by an external factor and may result from specific causes such as exposure to certain drugs, toxins, infections, strokes, spinal cord injuries, head injuries, or peripheral injuries. Dystonia has been reported to be associated with hyperactivity of cholinergic interneurons (Chl), which supply acetylcholine (Ach) to medium spiny neurons (MSNs). Overactivity of cholinergic interneurons leads to increased acetylcholine for signaling to medium spiny neurons and other nerve populations, resulting in dystonia. Currently available treatment options for patients with dystonia do not provide adequate therapeutic benefits to all patients and / or have significant adverse side effects.

[0004] Trihexyphenidyl-HCl (THP), a phenylpropylamine, was the first anticholinergic agent approved by the FDA in 1949. THP is a synthetic antispasmodic widely used in the treatment of patients with Parkinson's disease, including primary or idiopathic Parkinson's disease, secondary symptomatic Parkinson's disease (post-encephalitis, atherosclerotic, infection-induced, tumor-induced, trauma-induced, and drug-induced), and involuntary movements due to side effects of certain psychotropic 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 Parkinson's disease and for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenone. THP is widely used off-label for the treatment of certain types of dystonia. However, there are significant problems associated with using THP to treat dystonia and Parkinson's disease, including causing significant adverse side effects at doses typically used for treating dystonia, and current reports describe frequent THP administrations; each of these is attributed to poor patient compliance with THP treatment and associated poor treatment outcomes. [Overview of the project] [Problems that the invention aims to solve]

[0005] Therefore, there is a need for novel therapies and pharmaceutical compositions for the treatment of movement disorders, including dystonia. The present invention addresses this need and provides other related advantages. [Means for solving the problem]

[0006] overview The present invention provides therapeutic methods, pharmaceutical compositions, and unit-dose formulations for the treatment of 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 present invention provides a method for treating a movement disorder in a patient, comprising administering to the patient in need (i) an amount of a muscarinic acetylcholine receptor inhibitor effective for treating the movement disorder and (ii) an amount of a muscarinic acetylcholine receptor activator effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, thereby treating 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. The use of a combination of a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator reduces the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor and also provides the additional benefit of administering higher doses of the muscarinic acetylcholine receptor inhibitor to the patient while maintaining a patient-acceptable side effect profile. The use of a combination of a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator also allows the subject to take the combination agent and initiate treatment with a higher dose of the muscarinic receptor inhibitor than would be achieved with the muscarinic receptor inhibitor alone. Such combination agents also allow for lower doses of the muscarinic receptor inhibitor, such as subthermal doses before reaching a therapeutic dose, compared to the administration of the muscarinic receptor inhibitor alone.

[0007] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to the patient in need (i) an effective amount for treating the motor disorder and (ii) a muscarinic acetylcholine receptor activator that does not interfere with the therapeutic benefits of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder.

[0008] In one embodiment, the method comprises administering to a patient in need (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity in a therapeutically effective dose of at least 95% enantiomer excess, and (ii) a muscarinic acetylcholine receptor activator, thereby treating a motor disorder. The use of a combination of a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator reduces the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor and also provides the additional benefit of being able to administer a high dose of the muscarinic acetylcholine receptor inhibitor to the patient while maintaining a patient-acceptable side effect profile.

[0009] In one embodiment, the method comprises administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, procholinergic agents, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the second therapeutic agent is administered to the patient in an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

[0010] In one embodiment, an oral pharmaceutical composition is provided comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) a muscarinic acetylcholine receptor activator in an amount effective to reduce the frequency and / or intensity 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 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.

[0011] In one embodiment, an oral pharmaceutical composition is provided comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, and (iii) a pharmaceutically acceptable carrier, wherein the second therapeutic agent is present in an amount effective in reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

[0012] In one embodiment, a pharmaceutical composition is provided comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess, (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier.

[0013] In one embodiment, a pharmaceutical composition is provided comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess, (ii) a muscarinic acetylcholine receptor activator selected from racemic betanethol or a pharmaceutically acceptable salt thereof, and (iii) a pharmaceutically acceptable carrier.

[0014] In one embodiment, a pharmaceutical composition is provided comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess, (ii) a muscarinic acetylcholine receptor activator selected from (S)-bethanechol or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess, and (iii) a pharmaceutically acceptable carrier. The pharmaceutical composition can be formulated, for example, for oral administration.

[0015] In one embodiment, a pharmaceutical composition described herein is provided for use in pharmaceuticals. In one embodiment, a pharmaceutical composition described herein is provided for use in the treatment of a disorder described herein, such as a motor disorder. 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 one embodiment, trihexyphenidyl or a pharmaceutically acceptable salt thereof is racemic trihexyphenidyl. In one embodiment, trihexyphenidyl or a pharmaceutically acceptable salt thereof is (R)-trihexyphenidyl. In one embodiment, (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess. In one embodiment, betanethol or a pharmaceutically acceptable salt thereof is racemic betanethol. In one embodiment, betanethol or a pharmaceutically acceptable salt thereof is (S)-betanethol. In one embodiment, (S)-betanethol or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess.

[0016] In one embodiment, a combination is provided comprising a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator. In one embodiment, the combination is intended for use as a pharmaceutical. In one embodiment, the combination is intended for use in the treatment of disorders described herein, such as motor disorders. 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 one embodiment, trihexyphenidyl or a pharmaceutically acceptable salt thereof is racemic trihexyphenidyl. In one embodiment, trihexyphenidyl or a pharmaceutically acceptable salt thereof is (R)-trihexyphenidyl. In one embodiment, (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess. In one embodiment, betanethol or a pharmaceutically acceptable salt thereof is racemic betanethol. In one embodiment, betanethol or a pharmaceutically acceptable salt thereof is (S)-betanethol. In one embodiment, (S)-betanethol or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess. [Brief explanation of the drawing]

[0017] [Figure 1] This graph shows the results of an assay measuring the agonist activity of compound (S)-bethanechol chloride ((S)-BTC) against the human M1 muscarinic receptor in the presence of (R)-trihexyphenidyl-HCl ((R)-THP) (further details are provided in Example 5).

[0018] [Figure 2]This graph shows the change in the EC50 of (S)-BTC relative to the human M1 muscarinic receptor upon addition of (R)-THP (further details are provided in Example 5).

[0019] [Figure 3] This graph shows the concentrations of (S)-bethanechol in rat plasma, brain tissue, and cerebrospinal fluid after a single oral administration (further details are provided in Example 7).

[0020] [Figure 4] This graph shows the ratio of (S)-bethanechol in brain tissue compared to rat plasma after a single oral administration (further details are provided in Example 7).

[0021] [Figure 5] This graph illustrates the effects of various forms of trihexyphenidyl on haloperidol-induced catalepsy in rats 30 minutes after injection (further details are provided in Example 9).

[0022] [Figure 6] This graph shows the efficacy of (R)-THP and racemic THP in haloperidol-induced catalepsy assays at various doses (further details are provided in Example 9).

[0023] [Figure 7A-7C] This graph shows the efficacy and effectiveness of THP alone (Figure 7A), BTC alone (Figure 7B), and a combination of THP and BTC (Figure 7C) on electric field stimulation (EFS)-induced contractions in a guinea pig ileal myotenteric plexus longitudinal muscle (MPLM) strip (further details are provided in Example 10).

[0024] [Figure 8] This graph shows the effects of racemic THP alone, racemic BTC alone, and racemic THP administered in combination with racemic BTC on tear production (further details are provided in Example 11).

[0025] [Figures 9A-9F] Figure 9A is a series of graphs showing the 95% confidence intervals for each treatment group from Figure 8 (further details are provided in Example 11). Figure 9A shows the THP monotherapy group. Figure 9B shows the 1:1 THP:BTC combination treatment group. Figure 9C shows the 1:1:THP:BTC alternating 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 monotherapy group.

[0026] [Figure 10A-10B] This graph shows the plasma THP concentration (ng / mL) (Figure 10A) and plasma BTC concentration (ng / mL) (Figure 10B) in dogs when THP alone, BTC alone, and THP:BTC in various ratios were administered (further details are provided in Example 12).

[0027] [Figure 11] This graph shows the plasma exposure levels of racemic THP monotherapy compared to racemic BTC combination therapy (further details are provided in Example 13).

[0028] [Figures 12A-12B] This graph shows the plasma THP concentration (ng / mL) and the Visual Analog Scale (VAS), a common clinical indicator of dizziness, in human subjects after a single administration of 9 mg THP immediate-release (Figure 12A) and three consecutive administrations of 3 mg THP at 0, 2, and 4 hours (Figure 12B) (further details are provided in Example 14).

[0029] [Figures 13A-13B] This figure shows the plasma concentrations of racemic THP (indicated as PK, Figure 13A) and (R)-THP (indicated as PK, Figure 13B) (ng / mL) after administration of racemic THP in human subjects, and also includes a graph showing a quantitative index of dizziness using a visual analog scale (VAS, indicated as PD) (further details are provided in Example 14).

[0030] [Figures 14A-14B] These graphs show the enantiomer plasma exposure to R-THP and S-THP in humans at 0.5 hours (Figure 14A) and 9 hours (Figure 14B).

[0031] [Figure 15] This graph shows the enantiomer plasma exposure of R-THP as a fraction of total THP in dogs after oral and intravenous administration.

[0032] [Figure 16] This is a series of graphs showing the metabolite profiles of R-THP, S-THP, and racemic THP in human liver microsomes after 30-minute and 60-minute incubation. [Modes for carrying out the invention]

[0033] Detailed description The present invention provides therapeutic methods, pharmaceutical compositions, and unit-dose formulations for the treatment of movement disorders, such as using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator to treat dystonia. The use of a combination of a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator reduces the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor and also provides the further benefit of being able to administer high doses of the muscarinic acetylcholine receptor inhibitor to the patient while maintaining a patient-acceptable side effect profile. The implementation of the present invention utilizes conventional techniques of organic chemistry, pharmacology, molecular biology (including recombinant techniques), cell biology, biochemistry, and immunology, unless otherwise specified. Such techniques are described in literature such as “Comprehensive Organic Synthesis” (BM Trost & I. Fleming, eds., 1991-1992); “Handbook of experimental immunology” (DM Weir & CC Blackwell, eds.); “Current protocols in molecular biology” (FM Ausubel et al., eds., 1987, and periodic updates); and “Current protocols in immunology” (JE Coligan et al., eds., 1991).

[0034] Various aspects of the present invention are shown below in the sections; however, aspects of the present invention described in a particular section are not limited by any particular section. Furthermore, where a variable is not defined, the earlier definition of the variable takes precedence.

[0035] definition The compounds of the present invention include those generally described herein and are further described by the classes, subclasses and species disclosed herein. The following definitions used herein should apply unless otherwise specified. These definitions apply whether the terms are used alone or in combination with other terms, unless otherwise specified. Thus, the definition of "alkyl" applies to "alkyl" and "alkyl" parts such as "-O-alkyl". For the purposes of this invention, chemical elements are defined in the periodic table, CAS version, Handbook of Chemistry and Physics, 75 th The general principles of organic chemistry are identified according to the ed. Furthermore, the general principles of organic chemistry are found in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry”, 5 th It is listed in Ed., Ed.: Smith, MB and March, J., John Wiley & Sons, New York: 2001.

[0036] As used herein, the terms “aliphatic” or “aliphatic group” refer to a straight (i.e., unbranched), branched, substituted, or unsubstituted hydrocarbon chain that is fully saturated or contains one or more unsaturated units, with one bond site remaining on the rest of the molecule, or a monocyclic or bicyclic hydrocarbon (also referred to herein as “alicyclic”) that is fully saturated or contains one or more unsaturated units but is not aromatic. Unless otherwise specified, an aliphatic group contains 1 to 6 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1 to 5 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1 to 4 aliphatic carbon atoms. In yet another embodiment, an aliphatic group contains 1 to 3 aliphatic carbon atoms, and in yet another embodiment, an aliphatic group contains 1 to 2 aliphatic carbon atoms. In some embodiments, “alicyclic” refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more unsaturated units, but is not aromatic, with one bond site remaining on 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.

[0037] As used herein, the term “bicyclic ring” or “bicyclic ring system” refers to any bicyclic ring system having one or more atoms common between the two rings of the ring system, i.e., carbocyclic or heterocyclic, saturated or having one or more unsaturated units. Thus, this term includes all acceptable ring condensations, such as ortho condensations or spirocyclics. As used herein, the term “heterobicyclic” is a subset of “bicyclic” that requires the presence of one or more heteroatoms in one or both of the two rings. Such heteroatoms may be present at the ring junction and may be substituted as desired, and may be selected from nitrogen (including N-oxide), oxygen, sulfur (including oxidation forms such as sulfones and sulfonates), phosphorus (including oxidation forms such as phosphates), boron, etc. In one embodiment, the bicyclic group has 7 to 12 ring members and 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. As used herein, the term “bridged bicyclic” refers to any bicyclic ring system having at least one bridge, i.e., carbocyclic or heterocyclic, saturated or partially unsaturated. As defined by IUPAC, a “bridge” is an unbranched chain or valence bond of one or more atoms connecting two bridgeheads, where “bridgehead” is any skeletal atom of the ring system bonded to three or more skeletal atoms (other than hydrogen). In some embodiments, a bridged bicyclic group has 7 to 12 ring members and 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include the groups shown below, where each group is bonded to the rest of the molecule with any substituteable carbon or nitrogen atom. Unless otherwise specified, bridged bicyclic groups are optionally substituted with one or more substituents, as shown for aliphatic groups. In addition to or separately from this, any substituteable nitrogen in a bridged bicyclic group is optionally substituted. Exemplary bicyclic rings are: [ka] Includes.

[0038] An exemplary two-ring bridge is: [ka] Includes.

[0039] The term "lower alkyl" refers to a straight-chain or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl. 1-4 The term "heteroatom" means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (any oxidation state of nitrogen, sulfur, phosphorus, or silicon; any quaternized form of any basic nitrogen; replaceable nitrogen in a heterocyclic ring, e.g., as in N(3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR

[0040] (as in N-substituted pyrrolidinyl)). +

[0041] As used herein, the term "unsaturated" means that the moiety has one or more unsaturation units.

[0042] As used herein, the term "divalent C 1-8 (or C 1-6 ) saturated or unsaturated, straight-chain or branched, hydrocarbon chain" refers to a divalent alkylene, alkenylene, and alkynylene chain that is straight-chain or branched as defined herein.

[0043] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2) n -, where n is a positive integer, preferably 1 to 6, 1 to 4, 1 to 3, 1 to 2, or 2 to 3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced by substituents. Suitable substituents include those described below for substituted aliphatic groups.

[0044] The term "-(C0 alkylene)-" refers to a bond. Thus, the term "-(C 0-3 alkylene)-" includes a bond (i.e., C0) and a -(C 1-3 alkylene)- group.

[0045] The term "alkenylene" refers to a divalent 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 by substituents. Suitable substituents include the following for substituted aliphatic groups:

[0046] The term "halogen" refers to F, Cl, Br, or I.

[0047] The term “aryl,” used alone or as part of a larger term such as “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to a monocyclic or bicyclic ring system having a total of 5 to 14 ring members, where at least one ring in the system is aromatic and 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 embodiments, “aryl” refers to aromatic ring systems, including but not limited to phenyl, biphenyl, naphthyl, anthracyl, etc., which may hold one or more substituents. Also included in the scope of the term “aryl,” as it is used herein, are groups in which an aromatic ring is condensed with one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthoimidyl, phenantridinyl, or tetrahydronaphthyl.

[0048] The terms "heteroaryl" and "heteroaryl-", used alone or as part of a larger group, e.g., "heteroaryl" or "heteroaryl-", refer to a group having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; 6, 10, or 14 π electrons shared in a cyclic array; and having 1 to 5 heteroatoms in addition to carbon atoms. The term "heteroatom" refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur and any quaternized form of basic nitrogen. Heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridadinyl, pyrimidinyl, pyrazinyl, indolidinyl, prinyl, naphthilidinyl, and pteridinyl. As used herein, the terms “heteroaryl” and “hetero-” also include groups in which a heteroaromatic ring is condensed with one or more aryl, alicyclic, or heterocyclyl rings, and unless otherwise specified, the binding radical or point is one of the heteroaromatic rings or the rings to which the heteroaromatic rings are condensed. Non-restrictive examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolidinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, and tetrahydroisoquinolinyl. Heteroaryl groups can be monocyclic or bicyclic. The term "heteroaryl" can be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroaromatic," any of which may include a ring in which the group is optionally substituted. The term "heteroaralkyl" refers to an alkyl group substituted with a heteroaryl group, where the alkyl and heteroaryl moieties are optionally substituted independently.

[0049] The terms “heterocyclic,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” as used herein are interchangeable and refer to stable 5-7 member monocyclic or 7-10 member bicyclic heterocyclic portions that are saturated or partially unsaturated and have one or more, preferably 1-4, heteroatoms in addition to carbon atoms, as defined above. When referring to the ring atoms of a heterocyclic ring, the term “nitrogen” includes substituted nitrogen. For 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-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or + It can be NR (as in N-substituted pyrrolidinyl).

[0050] The heterocyclic ring can be bonded to any heteroatom or carbon side chain group that results in a stable structure, and any of the ring atoms may be substituted as desired. Examples of such saturated or partially unsaturated heterocyclic radicals include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenylpyrrolidinyl, 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 include groups in which a heterocyclyl ring, such as indolinyl, 3H-indolyl, chromanyl, phenantridinyl, or tetrahydroquinolinyl, is condensed with one or more aryl, heteroaryl, or alicyclic rings. The heterocyclyl group may be monocyclic or bicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted with a heterocyclyl, where the alkyl and heterocyclyl moieties are independently substituted as desired.

[0051] As used herein, the term "partially unsaturated" refers to a ring portion containing at least one double or triple bond. The term "partially unsaturated" is intended to include rings having multiple unsaturated moieties as defined herein, but not to include aryl or heteroaryl moieties.

[0052] The compounds of the present invention described herein may include “optionally substituted” portions. Generally, the term “substituted,” whether preceded by the term “optionally,” means that one or more hydrogens of the designated portion are replaced by appropriate substituents. Unless otherwise specified, an “optionally substituted” group may have appropriate substituents at each substitutedable position of the group, and when one or more nucleotides of a given structure can be replaced by one or more substituents selected from a particular group, the substituents may be identical or different at all positions. The substituent combinations intended by the present invention preferably result in the formation of stable or chemically feasible compounds. As used herein, the term “stable” means a compound that is substantially unchanged when subjected to conditions that enable production, detection, and, in some embodiments, recovery, purification, and use for one or more purposes disclosed herein.

[0053] Each desired substituent on the substituted carbon is a halogen;-(CH2) 0-4 R°;-(CH2) 0-4 OR°;-O(CH2) 0-4 R o -O-(CH2) 0-4 C(O)OR°;-(CH2) 0-4 CH(OR°)2;-(CH2) 0-4 SR°:R° may be substituted - (CH2) 0-4 It is acceptable for it to be substituted with Ph;R°-(CH2). 0-4 O(CH2) 0-1 It is acceptable for the pH to be substituted with R° - CH=CHPh; it is acceptable for the pH to be substituted with R° - (CH2) 0-4 O(CH2) 0-1 -pyridyl;-NO2;-CN;-N3;(CH2) 0-4 N(R°)2;-(CH2) 0-4N(R°)C(O)R°;-N(R°)C(S)R°;-(CH2) 0-4 N(R°)C(O)NR°2;N(R°)C(S)NR°2;-(CH2) 0-4 N(R°)C(O)OR°;-N(R°)N(R°)C(O)R°;N(R°)N(R°)C(O)NR°2;N(R°)N(R°)C(O)OR°;-(CH2) 0-4 C(O)R°;-C(S)R°;-(CH2) 0-4 C(O)OR°;-(CH2) 0-4 C(O)SR°;(CH2) 0-4 C(O)OSiR°3;-(CH2) 0-4 OC(O)R°;-OC(O)(CH2) 0-4 SR-, SC(S)SR°;-(CH2) 0-4 SC(O)R°;-(CH2) 0-4 C(O)NR°2;-C(S)NR°2;-C(S)SR°;-SC(S)SR°, (CH2) 0-4 OC(O)NR°2;C(O)N(OR°)R°;-C(O)C(O)R°;-C(O)CH2C(O)R°;-C(NOR°)R°;(CH2) 0-4 SSR°;-(CH2) 0-4 S(O)2R°;-(CH2) 0-4 S(O)2OR°;-(CH2) 0-4 OS(O)2R°;-S(O)2NR°2;-S(O)(NR°)R°;-S(O)2N=C(NR°2)2;(CH2) 0-4 S(O)R°;N(R°)S(O)2NR°2;-N(R°)S(O)2R°;-N(OR°)R°;-C(NH)NR°2;-P(O)2R°;P(O)R°2;OP(O)R°2;-OP(O)(OR°)2;SiR°3;-(C 1-4 Linear or branched alkylene) ON(R°)2; or -(C 1-4 A monovalent substituent independently selected from linear or branched alkylene (C(O)ON(R°)2).

[0054] Each R° independently contains hydrogen and C 1-6 Aliphatic, -CH2Ph, -O(CH2) 0-1Ph, -CH2- (5-6 member heteroaryl ring), or a 5-6 member saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the above definition, two independently existing R°s, together with an intervening atom, form a 3-12 member saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, where the saturated carbon atoms of R° may be substituted with divalent substituents selected from =O and =S; or each R° may optionally be a halogen, -(CH2) 0-2 R ● ,-(HaroR ● ), -(CH2) 0-2 OH, -(CH2) 0-2 Ure ● ,-(CH2) 0-2 CH(OR ● )2;O(HaroR ● ), -CN, -N3, -(CH2) 0-2 C(O)R ● ,-(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR ● ,-(CH2) 0-2 SR ● ,-(CH2) 0-2 SH, -(CH2) 0-2 NH2, -(CH2) 0-2 NHR ● ,-(CH2) 0-2 NR ● 2, -NO2, -SiR ● 3. -OSiR ● 3. C(O)SR ● ,-(C 1-4 (Linear or branched alkylene) C(O)OR ● , or -SSR ● It is substituted with a monovalent substituent selected independently of the original molecule.

[0055] Each R ● C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1Selected from 5- to 6-membered saturated, partially unsaturated or aryl rings having Ph or heteroatoms independently selected from 0 to 4 nitrogens, oxygens or sulfurs, each R ● is unsubstituted or, when halo is present before it, substituted only with one or more halogens; or the substituent at will on saturated carbon is =O, =S, =NNR * 2, =NNHC(O)R * 、=NNHC(O)OR * 、=NNHS(O)2R * 、=NR * 、=NOR * 、-O(C(R * 2)) 2-3 O-, or -S(C(R * 2)) 2-3 S- is a divalent substituent independently selected from, or the divalent substituent bonded to the vicinal substitutable carbon of the "substituted at will" group is -O(CR * 2) 2-3 O-, where R * is independently hydrogen, C 1-6 is selected from aliphatic or unsubstituted 5- to 6-membered saturated, partially unsaturated or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0056] R * When R 1-6 is 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, where each R ● is independently C 1-4 is aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or selected from 5- to 6-membered saturated, partially unsaturated or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, each R ●It is either unsubstituted or, when preceded by a halo, substituted by only one or more halogens.

[0057] Any desired substituent on the substituted nitrogen is independently -R † , -NR † 2, -C(O)R † , -C(O)OR † ,-C(O)C(O)R † -C(O)CH2C(O)R † S(O)2R † , S(O)2NR † 2, -C(S)NR † 2, -C(NH)NR † 2, or -N(R † )S(O)2R † And here, each R † Hydrogen and C are independent of each other. 1-6 Aliphatic, unsubstituted -OPh, or an unsubstituted 5-6 member saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two independently present R † R, together with the intervening atom, forms an unsubstituted 3-12 member saturated, partially unsaturated, or aryl mono or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; where R † C 1-6 When it is aliphatic, R † Halogen, -R (as requested) ● , (HaroR ● ), OH, -OR ● ,-O(HaroR ● ), -CN, -C(O)OH, -C(O)OR ● -NH2, -NHR ● , -NR ● 2, or -NO2 is substituted, where each R ● C is independent 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 A 5-6 member saturated, partially unsaturated, or aryl ring having a heteroatom independently selected from 0-4 nitrogen, oxygen, or sulfur atoms, each R ●It is either unsubstituted or, when preceded by a halo, substituted by only one or more halogens.

[0058] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that, within reasonable medical judgment, is free from excessive toxicity, irritation, or allergic reactions, is suitable for use in contact with human and lower animal tissues, and possesses a reasonable benefit / risk ratio. pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge et al. detail pharmaceutically acceptable salts in J. Pharmaceutical Sciences, 1977, 66, 1-19. pharmaceutically acceptable salts of the compounds of the present invention include those derived from appropriate inorganic and organic acids and bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or obtained by other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include adipine, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptone, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, and 2-hydroxyethanes. This includes ruhonate, 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, etc.

[0059] Furthermore, acids generally considered suitable for forming pharmaceutically useful salts from basic pharmaceutical compounds are listed, for example, in 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 et al., The Practice of Medicinal Chemistry (1996), Academic Press, New York; and The Orange Book (Food & Drug Administration, Washington, DC, available on their website).

[0060] Suitable base-derived salts include alkali metals, alkaline earth metals, ammonium, and N + (C 1-4 This includes alkyl) tetrasalts. Typical alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium. Further pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates, where appropriate.

[0061] Unless otherwise specified, the structures shown herein also include all isomeric forms of the structure (e.g., enantiomers, diastereomers, and geometric (or stereostructural) forms); for example, R and S configurations of each chiral center, Z and E double bond isomers, and Z and E stereostructural isomers. Thus, single stereochemical isomers of the compound, as well as mixtures of enantiomers, diastereomers, and geometric (or stereostructural) forms, are within the scope of the present invention. Unless otherwise specified, all tautomeric forms of the compound of the present invention are within the scope of the present invention. The present invention includes compounds that differ only by the presence of one or more isotopically enriched atoms. For example, substitution of hydrogen with deuterium or tritium, or carbon 13 C or 14 Compounds having this structure, including substitution with 1C-enriched carbon, are within the scope of the present invention. Such compounds are useful, for example, as analytical tools, probes in biological assays, or therapeutic agents according to the present invention.

[0062] Diastereomer mixtures can be separated into individual diastereomers based on physicochemical differences by methods known to those skilled in the art, such as chromatography and / or fractional crystallization. Enantiomers can be separated by converting the enantiomer mixture into a diastereomer mixture by reaction with a suitable optically active compound (e.g., a chiral auxiliary such as a chiral alcohol or moscheric acid chloride), separating the diastereomers, and converting the individual diastereomers into their corresponding pure enantiomers (e.g., by hydrolysis). Alternatively, specific enantiomers of the compounds of the present invention can be produced by asymmetric synthesis. Furthermore, when the molecule contains a basic functional group (e.g., amino) or an acidic functional group (e.g., carboxylic acid), a diastereomer salt can be formed with a suitable optically active acid or base, and the diastereomer thus formed can be separated by fractional crystallization or chromatographic means known in the art, followed by the recovery of the pure enantiomer.

[0063] The individual stereoisomers of the compounds of the present invention may, for example, exist substantially without other isomers, or may be mixed with all or other selected stereoisomers, for example, as a racemate. The chiral centers of the compounds of the present invention may have an S or R configuration as defined in the IUPAC 1974 Recommendations. Furthermore, insofar as the compounds described herein may exist as atropisomers (e.g., substituted biaryls), all forms of such atropisomers are considered part of the present invention.

[0064] Chemical names, common names, and chemical structures may be used interchangeably to describe the same structure. If a chemical compound is described by both chemical structure and chemical name, and there is ambiguity between the structure and the name, the structure takes precedence. It should be noted that any carbon and heteroatoms whose valence is not satisfied in the letters, schemes, examples, and tables herein are assumed to have a sufficient number of hydrogen atoms to satisfy their valence.

[0065] The singular expressions used here mean "one or more," and unless inappropriate from the context, include plurals.

[0066] The term "alkyl" here refers to C1-C 12 Alkyl, C1-C 10 Alkyl and C1-C6 alkyl groups are saturated linear or branched hydrocarbons, such as linear or branched groups with 1 to 12, 1 to 10, or 1 to 6 carbon atoms. Exemplary alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, and others.

[0067] The term "cycloalkyl" refers to a monovalent saturated cyclic, bicyclic, or bridged cyclic (e.g., adamantyl) hydrocarbon group of 3 to 12, 3 to 8, 4 to 8, or 4 to 6 carbon atoms, derived from cycloalkanes, for example, referred to as "C3-C6 cycloalkyl." Exemplary cycloalkyls include cyclohexyl, cyclopentyl, cyclobutyl, and cyclopropyl. The term "cycloalkylene" refers to a divalent cycloalkyl group.

[0068] symbol [ka] This indicates a connection point.

[0069] When any substituent or variable group is present more than once in any component or compound of the present invention, the definition of each case shall be independent of the definitions of all other cases unless otherwise specified.

[0070] One or more compounds of the present invention can exist in unsolvated and solvated forms in pharmaceutically acceptable solvents such as water and ethanol, and the present invention is intended to encompass both solvated and unsolvated forms. “Solvated” means the physical association of a compound of the present invention with one or more solvent molecules. This physical association includes varying degrees of ionic and covalent bonding, including hydrogen bonding. In some cases, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvated can be isolated. “Solvated” includes both liquid phase and isolable solvated forms. Non-limiting examples of suitable solvated forms include ethanolates and methanolates. “Hydrate” is a solvated form in which the solvent molecule is H2O.

[0071] The terms “subject” and “patient” as used herein are interchangeable and refer to organisms treated by the methods of the present invention. Such organisms preferably include mammals (e.g., mice, apes, horses, cattle, pigs, dogs, cats, etc.), and most preferably include humans.

[0072] The term “IC 50 " is recognized in this field and refers to the concentration of a compound required to achieve 50% inhibition of the target.

[0073] The term “EC 50 " is recognized in this field and refers to the concentration of a compound required to achieve 50% activation of the target.

[0074] As used herein, the terms “effective dose” or “effective amount” are interchangeable and refer to the amount of compound sufficient to produce a beneficial or desired outcome (e.g., therapeutic, ameliorative, inhibitory, or prophylactic). An effective dose is administered in one or more doses, applications, or dosages and is not intended to be limited to a specific formulation or route of administration. As used herein, the terms “to treat” and “treatment” include any effect that results in improvement of a condition, disease, disorder, etc., such as reduction, mitigation, regulation, improvement or elimination, or improvement of its symptoms.

[0075] As used herein, the term "pharmaceutical composition" refers to a combination of an activator and an inert or active carrier that makes the composition particularly suitable for in vivo or ex vivo diagnostic or therapeutic applications.

[0076] As used herein, the term “pharmaceutically acceptable carrier” refers to any of the standard pharmaceutical carriers, such as phosphate-buffered saline, water, emulsions (e.g., oil / water or water / oil emulsions), and various types of wetting agents. The composition may also include stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see, for example, Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA

[1975] .

[0077] For therapeutic purposes, salts of the compounds of the present invention are intended to be pharmaceutically acceptable. However, salts of pharmaceutically unacceptable acids and bases may also be useful, for example, in the production or purification of pharmaceutically acceptable compounds.

[0078] Furthermore, when the compounds of the present invention contain both a basic moiety (e.g., pyridine or imidazole, but not limited to these) and an acidic moiety (e.g., a carboxylic acid, but not limited to these), zwitterions ("intramolecular salts") may be formed. Such acidic and basic salts used within the scope of the present invention are pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts. Salts of such compounds of the present invention may be formed, for example, by reacting the compound of the present invention with a certain amount, for example, an equivalent amount of acid or base, in a medium such as one that precipitates salts or an aqueous medium, and then freeze-drying.

[0079] As used herein, the term "THP" refers to trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, "Rac-THP" or "racemic THP" refers to racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, "(R)-THP" or "R-THP" refers to (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, "(S)-THP" or "S-THP" refers to (S)-trihexyphenidyl or a pharmaceutically acceptable salt thereof. As used herein, the term "BTC" refers to bethanechol or a pharmaceutically acceptable salt thereof. As used herein, "Rac-BTC" or "racemic BTC" refers to racemic bethanechol or a pharmaceutically acceptable salt thereof. As used herein, "(R)-BTC" or "R-BTC" refers to (R)-bethanechol or a pharmaceutically acceptable salt thereof. As used herein, "(S)-BTC" or "S-BTC" refers to (S)-bethanechol or a pharmaceutically acceptable salt thereof.

[0080] The terms "intensity" and "severity" used herein are interchangeable.

[0081] Throughout this specification, when a composition is described as having, containing, or encompassing a particular component, or when a process and method is described as having, containing, or encompassing a particular step, it is intended that there are compositions of the present invention that are essentially composed of or consist of the described component, and processes and methods of the present invention that are essentially composed of or consist of the described processing step.

[0082] Generally speaking, composition specified by percentage is determined by weight unless otherwise specified.

[0083] I. Treatment This invention provides a therapeutic method using a muscarinic acetylcholine receptor inhibitor in combination with a muscarinic acetylcholine receptor activator. This therapeutic method is useful for treating motor disorders. Various aspects and embodiments of the therapeutic method are described in the following sections. The sections are arranged in a convenient order, and the information in one section is not limited to that section but may apply to methods in other sections.

[0084] A. First treatment One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder.

[0085] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder, and (ii) an amount effective for reducing the frequency and intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

[0086] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder, and (ii) an amount effective for reducing the frequency or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

[0087] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder, and (ii) an amount effective for reducing the intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, to the subject.

[0088] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder, and (ii) an amount effective for reducing the frequency of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

[0089] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0090] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency and intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0091] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0092] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0093] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

[0094] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0095] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency and intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0096] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0097] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0098] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0099] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemitebethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0100] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency and intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0101] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0102] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0103] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0104] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors in an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor activator, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor activator is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0105] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0106] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0107] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0108] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0109] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor in an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor activator, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor activator is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemitebethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0110] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0111] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0112] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0113] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0114] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0115] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency and intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0116] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0117] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0118] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0119] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0120] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency and intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0121] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0122] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0123] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemitebethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0124] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors in an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0125] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0126] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0127] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0128] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0129] One aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor in an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor activator, thereby treating the motor disorder, wherein the muscarinic acetylcholine receptor activator is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemitebethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0130] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0131] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0132] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0133] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from a muscarinic acetylcholine receptor activator, a cholinergic promoter, and an acetylcholinesterase inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic bethanechol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:10.

[0134] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio of about 1:1.1 to about 1:20.

[0135] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, the muscarinic acetylcholine receptor inhibitor and the muscarinic acetylcholine receptor activator are administered in a weight ratio greater than 1:1, and the muscarinic acetylcholine receptor activator is administered in excess of the muscarinic acetylcholine receptor inhibitor.

[0136] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency of at least one adverse effect of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, wherein a larger amount of the muscarinic acetylcholine receptor activator is administered compared to the amount of the muscarinic acetylcholine receptor inhibitor administered.

[0137] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a muscarinic receptor activator, wherein the amount of the muscarinic acetylcholine receptor inhibitor is at a dose level insufficient to reach an effective dose when administered in the absence of the muscarinic receptor activator.

[0138] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the amount of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an effective dose when administered in the absence of the muscarinic receptor activator.

[0139] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the dose of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof is about 50% lower than the dose of racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the dose level of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof is insufficient to reach an effective dose when administered in the absence of a muscarinic receptor activator.

[0140] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the amount of racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an effective dose when administered in the absence of the muscarinic receptor activator.

[0141] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an effective dose when administered in the absence of a muscarinic receptor activator.

[0142] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, 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 known to those skilled in the art in combination with a muscarinic receptor activator, the subject experiences more frequent, more intense, and / or more severe adverse effects compared to a subject administered a standard, monotherapy dose of a muscarinic acetylcholine receptor inhibitor.

[0143] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) (R)-trihexyphenidyl or a 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, known to those skilled in the art, in combination with a muscarinic receptor activator, the subject experiences more frequent, more intense, and / or more severe adverse effects compared to a subject administered a standard, monotherapy dose of (R)-trihexyphenidyl alone.

[0144] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a pharmaceutically acceptable salt thereof and (ii) a muscarinic receptor activator, wherein the subject experiences more frequent, more intense, and / or more severe adverse effects when administered in combination with a muscarinic receptor activator in a standard, monotherapy dose known to those skilled in the art, compared to a subject administered with a standard, monotherapy dose of racemitrihexyphenidyl alone.

[0145] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein if the subject is administered a standard, monotherapy dose of a muscarinic acetylcholine receptor inhibitor known to those skilled in the art in combination with a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, the subject experiences more frequent, more intense, and / or more severe adverse effects compared to a subject administered a standard dose of a muscarinic acetylcholine receptor inhibitor.

[0146] The method may be characterized by further characteristics such as the identification of muscarinic acetylcholine receptor inhibitors, the identification of muscarinic acetylcholine receptor activators, the order of administration, and other properties which are described in more detail here.

[0147] Muscarinic acetylcholine receptor inhibitors The method can be characterized by the identification of muscarinic acetylcholine receptor inhibitors. For example, in one embodiment, muscarinic acetylcholine receptor inhibitors are distributed to the central and peripheral nervous systems of the patient.

[0148] In one embodiment, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl. In one embodiment, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl hydrochloride.

[0149] In one embodiment, the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl. In one embodiment, the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl hydrochloride.

[0150] In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl hydrochloride.

[0151] In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 90% enantiomer excess, or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 99% enantiomer excess, or a pharmaceutically acceptable salt thereof.

[0152] In one embodiment, (a) the muscarinic acetylcholine receptor activator is racemic betanethol or a pharmaceutically acceptable salt thereof, and (b) the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

[0153] In one embodiment, muscarinic acetylcholine receptor inhibitors include acridinium bromide, acridinium bromide / formoterol, acotiamide, AH 9700, albamelin, AQRA 721, AQRA 741, AZD 9164, BIBN 99, CEB 1957, clozapine, darenzepine, dalifenacin, darotropium bromide, dextrorotatory mequitamium iodide, ebeinon, esoxybutynin, espatropart, etopropazine, fesoterodine, glycopyrrolate / indacaterol, glycopyrronium bromide, GSK 1160724, GSK 202405, GSK 573719, GSK 656398, GSK 961081, GYKI 46903, Methyl homatropine bromide, Imidafenacin, Glycopyrrolate, Ipratropium bromide, Ipratropium bromide / Xylometazolin, J 104129, J 106366, L 696986, LAS 35201, Levosalbutamol / Ipratropium Inhalation Solution, Liliodenine, LK 12, Mequitamium iodide, Methanetheline, Methanetheline bromide, Methoscopolamine 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, Oxybutynin transmucosal, Oxybutynin vaginal, PG 1000, Pirenzepine ophthalmic, Pimenol, PNU 200577, Promethazine / Hydrocodone / Paracetamol, Propantheline, Propantheline bromide, Propiverine, PSD 506, PTAC, QAT 370, FF2-Nuada, Levatropate, Rispenzepine, RL 315535, RO 465934, SCH 211803, SCH 57790, Scopolamine intranasal, Scopolamine transmucosal, Secoberin, S-ET 126, Syntropium bromide, Solifenacin, Solifenacin / Tamsulosin, SVT 40776, TD 6301, Terenzepine, Temibelin, Tiotropium bromide, Tolterodine, Tolterodine / Tamsulosin, Tropenzilium, Trospium chloride, V 0162, YM 35636, YM 46303, YM53705, YM 58790, or zamifenacin, or any pharmaceutically acceptable salt thereof.

[0154] B. Second treatment Another aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having a stereochemical purity of at least 95% enantiomer excess, and (ii) a muscarinic acetylcholine receptor activator, thereby treating the motor disorder.

[0155] The method may be characterized by further characteristics such as the amount of muscarinic acetylcholine receptor activator administered to the patient, the identification of the muscarinic acetylcholine receptor activator, the order of administration, and other properties which are described in more detail here.

[0156] In one embodiment, a muscarinic acetylcholine receptor activator is administered to the patient in a dose effective in reducing the side effects of a muscarinic acetylcholine receptor inhibitor.

[0157] C. Third treatment method Another aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering to a patient in need (i) a muscarinic acetylcholine receptor inhibitor and (ii) a muscarinic acetylcholine receptor activator, thereby treating the motor disorder.

[0158] In one aspect, muscarinic acetylcholine receptor activators do not negate the therapeutic benefits of muscarinic acetylcholine receptor inhibitors for treating motor disorders.

[0159] The method may be characterized by further characteristics such as the identification of muscarinic acetylcholine receptor inhibitors, the identification of muscarinic acetylcholine receptor activators, the order of administration, and other properties which are described in more detail here.

[0160] D. Fourth treatment method Another aspect of the present invention provides a method for treating a motor disorder in a patient, comprising administering a single enantiomer of a muscarinic acetylcholine receptor inhibitor to a patient in need thereof, wherein the enantiomer has a stereochemical purity of at least 90% enantiomer excess.

[0161] E. Fifth treatment method In one embodiment, a method is provided for treating a motor disorder in a patient, comprising administering to the patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the second therapeutic agent is administered to the patient in an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

[0162] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of the muscarinic acetylcholine receptor inhibitor is at a dose level insufficient to reach an effective dose when administered in the absence of the second therapeutic agent.

[0163] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an effective dose when administered in the absence of the second therapeutic agent.

[0164] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof and the amount of the muscarinic acetylcholine receptor inhibitor are at dose levels insufficient to reach an effective dose when administered in the absence of the second therapeutic agent.

[0165] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of the muscarinic acetylcholine receptor inhibitor is at a dose level insufficient to reach an effective dose when administered in the absence of the second therapeutic agent, and the dose of the muscarinic acetylcholine receptor inhibitor, when administered in combination with a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, reduces the frequency, intensity, and / or severity of at least one peripheral nervous system adverse effect.

[0166] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof is at a dose level insufficient to reach an effective dose when administered in the absence of the second therapeutic agent, and the dose of (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, when administered in combination with a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, reduces the frequency, intensity, and / or severity of at least one peripheral nervous system adverse effect.

[0167] In one embodiment, the present invention provides a method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) a pharmaceutically acceptable salt thereof and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the amount of racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof and the amount of a muscarinic acetylcholine receptor inhibitor are at a dose level insufficient to reach an effective dose when administered in the absence of the second therapeutic agent, and the amount of racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof, when administered in combination with a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, reduces the frequency, intensity, and / or severity of at least one peripheral nervous system adverse effect.

[0168] In one embodiment, the second therapeutic agent is a cholinergic promoter. In another embodiment, the second therapeutic agent is an acetylcholinesterase inhibitor. In another embodiment, the second therapeutic agent is pyridostigmine, neostigmine, physostigmine, edrophonium, or a pharmaceutically acceptable salt thereof. In another embodiment, the second therapeutic agent is distigmine bromide.

[0169] Muscarinic acetylcholine receptor inhibitors The method can be characterized by the identification of muscarinic acetylcholine receptor inhibitors. For example, in one embodiment, muscarinic acetylcholine receptor inhibitors are distributed to the central and peripheral nervous systems of the patient.

[0170] In one embodiment, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl. In one embodiment, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl hydrochloride.

[0171] In one embodiment, the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl. In one embodiment, the muscarinic acetylcholine receptor inhibitor is racemitrihexyphenidyl hydrochloride.

[0172] In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl hydrochloride.

[0173] In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 90% enantiomer excess, or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof. In one embodiment, the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 99% enantiomer excess, or a pharmaceutically acceptable salt thereof.

[0174] In one embodiment, the patient experiences no adverse side effects from the second treatment. In another embodiment, the patient experiences no adverse side effects from the muscarinic acetylcholine receptor activator.

[0175] F. Further embodiments of the first, second, third, fourth, and fifth treatments Further embodiments of the first, second, third, and fourth treatments are described below. These include, for example, the identification of muscarinic acetylcholine receptor activators, administration characteristics, motor disorder identification, and patient identification.

[0176] Muscarinic acetylcholine receptor activators The method can be characterized by the identification of muscarinic acetylcholine receptor activators. For example, in one embodiment, the muscarinic acetylcholine receptor activators are primarily distributed to the patient's peripheral nervous system.

[0177] In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is 1:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 2:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 3:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 4:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 5:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 8:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 10:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 15:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 20:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 50 to 1.In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 75:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 100:1. In one embodiment, the molar ratio of (i) muscarinic acetylcholine receptor activators present in the patient's peripheral nervous system to (ii) muscarinic acetylcholine receptor activators present in the patient's central nervous system is at least 1,000:1.

[0178] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.1 to approximately 1:20. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.2 to approximately 1:19.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.3 to approximately 1:19.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.4 to approximately 1:19.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.5 to approximately 1:19.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.6 to approximately 1:19.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.7 to approximately 1:19.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.8 to approximately 1:19.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.9 to approximately 1:19.2. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2 to approximately 1:19.1.

[0179] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.1 to approximately 1:19. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.2 to approximately 1:18.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.3 to approximately 1:18.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.4 to approximately 1:18.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.5 to approximately 1:18.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.6 to approximately 1:18.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.7 to approximately 1:18.4. In another embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.8 to approximately 1:18.3. In yet another embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.9 to approximately 1:18.2.

[0180] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3 to approximately 1:18.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.1 to approximately 1:18. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.2 to approximately 1:17.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.3 to approximately 1:17.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.4 to approximately 1:17.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.5 to approximately 1:17.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.6 to approximately 1:17.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.7 to approximately 1:17.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.8 to approximately 1:17.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.9 to approximately 1:17.2.

[0181] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4 to approximately 1:17.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.1 to approximately 1:17. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.2 to approximately 1:16.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.3 to approximately 1:16.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.4 to approximately 1:16.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.5 to approximately 1:16.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.6 to approximately 1:16.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.7 to approximately 1:16.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.8 to approximately 1:16.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.9 to approximately 1:16.2.

[0182] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5 to approximately 1:16.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.1 to approximately 1:16. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.2 to approximately 1:15.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.3 to approximately 1:15.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.4 to approximately 1:15.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.5 to approximately 1:15.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.6 to approximately 1:15.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.7 to approximately 1:15.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.8 to approximately 1:15.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.9 to approximately 1:15.2.

[0183] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6 to approximately 1:15.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.1 to approximately 1:15. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.2 to approximately 1:14.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.3 to approximately 1:14.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.4 to approximately 1:14.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.5 to approximately 1:14.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.6 to approximately 1:14.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.7 to approximately 1:14.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.8 to approximately 1:14.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6.9 to approximately 1:14.2.

[0184] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7 to approximately 1:14.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.1 to approximately 1:14. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.2 to approximately 1:13.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.3 to approximately 1:13.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.4 to approximately 1:13.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.5 to approximately 1:13.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.6 to approximately 1:13.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.7 to approximately 1:13.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.8 to approximately 1:13.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7.9 to approximately 1:13.2.

[0185] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8 to approximately 1:13.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.1 to approximately 1:13. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.2 to approximately 1:12.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.3 to approximately 1:12.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.4 to approximately 1:12.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.5 to approximately 1:12.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.6 to approximately 1:12.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.7 to approximately 1:12.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.8 to approximately 1:12.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8.9 to approximately 1:12.2.

[0186] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9 to approximately 1:12.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.1 to approximately 1:13. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.2 to approximately 1:11.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.3 to approximately 1:11.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.4 to approximately 1:11.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.5 to approximately 1:11.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.6 to approximately 1:11.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.7 to approximately 1:11.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.8 to approximately 1:11.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9.9 to approximately 1:11.2.

[0187] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10 to approximately 1:11.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10.1 to approximately 1:11. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10.2 to approximately 1:10.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10.3 to approximately 1:10.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10.4 to approximately 1:10.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10.5 to approximately 1:10.6.

[0188] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3 to approximately 1:7.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.1 to approximately 1:6.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.2 to approximately 1:6.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.3 to approximately 1:6.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.4 to approximately 1:6.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.5 to approximately 1:6.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.6 to approximately 1:6.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.7 to approximately 1:6.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.8 to approximately 1:6.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.9 to approximately 1:6.2.

[0189] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4 to approximately 1:6.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.1 to approximately 1:5.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.2 to approximately 1:5.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.3 to approximately 1:5.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.4 to approximately 1:5.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.5 to approximately 1:5.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.6 to approximately 1:5.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.7 to approximately 1:5.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.8 to approximately 1:5.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.9 to approximately 1:5.2. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5 to approximately 1:5.1.

[0190] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.1 to approximately 1:10. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.2 to approximately 1:9.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.3 to approximately 1:9.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.4 to approximately 1:9.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.5 to approximately 1:9.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.6 to approximately 1:9.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.7 to approximately 1:9.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.8 to approximately 1:9.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.9 to approximately 1:9.2. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2 to approximately 1:9.1.

[0191] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.1 to approximately 1:9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.2 to approximately 1:8.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.3 to approximately 1:8.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.4 to approximately 1:8.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.5 to approximately 1:8.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.6 to approximately 1:8.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.7 to approximately 1:8.4. In another embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.8 to approximately 1:8.3. In yet another embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2.9 to approximately 1:8.2.

[0192] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3 to approximately 1:8.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.1 to approximately 1:8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.2 to approximately 1:7.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.3 to approximately 1:7.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.4 to approximately 1:7.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.5 to approximately 1:7.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.6 to approximately 1:7.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.7 to approximately 1:7.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.8 to approximately 1:7.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3.9 to approximately 1:7.2.

[0193] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4 to approximately 1:7.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.1 to approximately 1:7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.2 to approximately 1:6.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.3 to approximately 1:6.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.4 to approximately 1:6.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.5 to approximately 1:6.6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.6 to approximately 1:6.5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.7 to approximately 1:6.4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.8 to approximately 1:6.3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4.9 to approximately 1:6.2.

[0194] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5 to approximately 1:6.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.1 to approximately 1:6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.2 to approximately 1:5.9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.3 to approximately 1:5.8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.4 to approximately 1:5.7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5.5 to approximately 1:5.6.

[0195] In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>1. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>2. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>3. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>4. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>5. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>6. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>7. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>8. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>9. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>10. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>11. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>12. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>13. In one embodiment, the weight ratio of administered (i) racemic THP to (ii) racemic BTC is approximately 1:>14. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:>15. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:>16. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:>17. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:>18. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:>19. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:>20.

[0196] In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:1.1. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:2. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:3. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:4. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:5. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:6. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:7. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:8. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:9. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:10. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:11. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:12. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:13. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:14. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:15. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:16. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:17. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:18. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:19. In one embodiment, the weight ratio of (i) racemic THP to (ii) racemic BTC administered is approximately 1:20.

[0197] In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:4 to 1:40. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:5 to 1:39. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:6 to 1:38. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:7 to 1:37. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:8 to 1:36. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:9 to 1:35. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:10 to 1:34. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:11 to 1:33. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:12 to 1:32. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:13 to 1:31. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:14 to 1:30. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:15 to 1:29. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:16 to 1:28. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:17 to 1:27. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:18 to 1:26. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:19 to 1:25. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:20 to 1:24. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:21 to 1:23.

[0198] In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:4. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:5. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:6. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:7. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:8. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:9. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:10. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:11. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:12. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:13. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:14. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:15. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:16. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:17. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:18. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:19. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:20. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:21. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:22. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:23.In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:24. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:25. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:26. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:27. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:28. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:29. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:30. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:31. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:32. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:33. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:34. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:35. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:36. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:37. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:38. In another embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:39. In yet another embodiment, the weight ratio of administered (i)(R)-THP to (ii) racemic BTC is approximately 1:40.

[0199] In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:2 to 1:20. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:3 to 1:19. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:4 to 1:18. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:5 to 1:17. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:6 to 1:16. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:7 to 1:15. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:8 to approximately 1:14. In another embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:9 to approximately 1:13. In yet another embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:10 to approximately 1:12.

[0200] In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:2. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:3. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:4. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:5. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:6. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:7. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:8. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:9. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:10. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:11. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:12. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:13. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:14. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:15. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:16. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:17. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:18. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:19. In one embodiment, the weight ratio of administered (i)(R)-THP to (ii)(S)-BTC is approximately 1:20.

[0201] In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:1 to approximately 1:40. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:2 to approximately 1:39. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:3 to approximately 1:38. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:4 to approximately 1:37. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:5 to approximately 1:36. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:6 to approximately 1:35. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:7 to approximately 1:34. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:8 to approximately 1:33. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:9 to approximately 1:32. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:10 to approximately 1:31. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:11 to approximately 1:30. In another embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:12 to approximately 1:29.In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:13 to approximately 1:28. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:14 to approximately 1:27. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:15 to approximately 1:26. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:16 to approximately 1:25. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:17 to approximately 1:24. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:18 to approximately 1:23. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:19 to approximately 1:22. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:20 to approximately 1:21. In one embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof.

[0202] In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:2 to approximately 1:8. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:3 to approximately 1:7. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:4 to approximately 1:6. In one embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof.

[0203] In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:1.1. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:2. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:3. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:4. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:5. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:6. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:7. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:8. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:9. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:10. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:11. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:12. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:13.In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:14. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:15. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:16. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:17. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:18. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:19. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:20. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:21. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:22. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:23. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:24. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:25. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:26.In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:27. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:28. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:29. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:30. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:31. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:32. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:33. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:34. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:35. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:36. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:37. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:38. In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:39.In one embodiment, the weight ratio of (i) muscarinic acetylcholine receptor inhibitor to (ii) muscarinic acetylcholine receptor activator administered is approximately 1:40. In one embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof.

[0204] In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:28 ng / mL to approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:29 ng / mL to approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration.In one embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0205] In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:28 ng / mL to approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:29 ng / mL to approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration.In one embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0206] In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:28 ng / mL to approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:29 ng / mL to approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration.In one embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0207] In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:20 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:21 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:22 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:23 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:24 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:25 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:26 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:27 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:28 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:29 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:30 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:37 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 4 hours to 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 5 hours to 12 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration.In one embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0208] In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:20 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:21 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:22 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:23 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:24 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:25 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:26 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:27 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:28 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:29 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:30 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:37 ng / mL after administration.In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 4 hours to 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 5 hours to 12 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration.In one embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0209] In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:20 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:21 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:22 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:23 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:24 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:25 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:26 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:27 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:28 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:29 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:30 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:36 ng / mL after administration.In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP to (ii)(S)-BTC is approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 4 to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration.In one embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0210] In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In another embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In yet another embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In another embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:28 ng / mL to approximately 1:32 ng / mL post-administration. In another embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:29 ng / mL to approximately 1:31 ng / mL post-administration. In another embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof. In another embodiment, the serum concentration ratio was determined approximately 30 minutes to approximately 24 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour to approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours to approximately 20 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 3 to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration.In one embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0211] In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In another embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration.In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:28 ng / mL to approximately 1:32 ng / mL post-administration. In another embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:29 ng / mL to approximately 1:31 ng / mL post-administration. In another embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof. In another embodiment, the serum concentration ratio was determined approximately 30 minutes to approximately 24 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour to approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours to approximately 20 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 3 to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration.In certain embodiments, the serum concentration ratio was determined at about 13 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 14 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 15 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 16 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 17 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 18 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 19 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 20 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 21 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 22 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 23 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 24 hours after administration.

[0212] In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In another embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In another embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:28 ng / mL to approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:29 ng / mL to approximately 1:31 ng / mL after administration. In some embodiments, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof. In some embodiments, the serum concentration ratio was determined approximately 30 minutes to 24 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 1 hour to 22 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 2 hours to 20 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 3 hours to 17 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 4 hours to 15 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 5 hours to 12 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 6 hours to 10 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 7 hours to 9 hours after administration. In some embodiments, the serum concentration ratio was determined approximately 30 minutes after administration. In some embodiments, the serum concentration ratio was determined approximately 1 hour after administration. In one embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration.In one embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In yet another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0213] In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:20 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:21 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:22 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:23 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:24 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:25 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:26 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:27 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:28 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:29 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:30 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:37 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:38 ng / mL post-administration. In another embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:39 ng / mL post-administration. In another embodiment, the serum concentration ratio of (i) racemic THP to (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:40 ng / mL post-administration. In another embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof. In another embodiment, the serum concentration ratio was determined approximately 30 minutes to approximately 24 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 1 to 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 to 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In yet another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In yet another embodiment, the serum concentration ratio was determined approximately 9 hours after administration.In certain embodiments, the serum concentration ratio was determined at about 10 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 11 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 12 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 13 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 14 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 15 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 16 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 17 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 18 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 19 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 20 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 21 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 22 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 23 hours after administration. In certain embodiments, the serum concentration ratio was determined at about 24 hours after administration.

[0214] In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:20 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:21 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:22 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:23 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:24 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:25 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:26 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:27 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:28 ng / mL after administration.In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:29 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:30 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:35 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:37 ng / mL after administration.In one embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:38 ng / mL post-administration. In another embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:39 ng / mL post-administration. In another embodiment, the serum concentration ratio of (i)(R)-THP versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:40 ng / mL post-administration. In another embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof. In another embodiment, the serum concentration ratio was determined approximately 30 minutes to approximately 24 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 1 to 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 2 to 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 to 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 to 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 to 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In yet another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In yet another embodiment, the serum concentration ratio was determined approximately 9 hours after administration.In one embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0215] In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:20 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:21 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:22 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:23 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:24 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:25 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:26 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:27 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:28 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:29 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:30 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:31 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:32 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:33 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:34 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic agents, and acetylcholinesterase inhibitors is approximately 1:35 ng / mL after administration.In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:36 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:37 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:38 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:39 ng / mL after administration. In one embodiment, the serum concentration ratio of (i) a muscarinic acetylcholine receptor inhibitor versus (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors is approximately 1:40 ng / mL post-administration. In one embodiment, the muscarinic acetylcholine receptor inhibitor is selected from scopolamine, benztropine, and etopropazine or a pharmaceutically acceptable salt thereof. In one embodiment, the serum concentration ratio was determined approximately 30 minutes to approximately 24 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 1 hour to approximately 22 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 2 hours to approximately 20 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 3 hours to approximately 17 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 4 hours to approximately 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 5 hours to approximately 12 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 6 to 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 to 9 hours after administration. In yet another embodiment, the serum concentration ratio was determined approximately 30 minutes after administration.In one embodiment, the serum concentration ratio was determined approximately 1 hour after administration. In another embodiment, the serum concentration ratio was determined approximately 2 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 3 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 4 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 5 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 6 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 7 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 8 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 9 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 10 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 11 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 12 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 13 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 14 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 15 hours after administration. In one embodiment, the serum concentration ratio was determined approximately 16 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 17 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 18 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 19 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 20 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 21 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 22 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 23 hours after administration. In another embodiment, the serum concentration ratio was determined approximately 24 hours after administration.

[0216] In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 20 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 19 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 18 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 17 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 16 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 15 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 14 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 13 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 12 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 10 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 9 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 8 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 7 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 6 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 5 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 4 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitor is less than 3 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is less than 2 ng / mL / hour.In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is less than 1 ng / mL / hour.

[0217] In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 1 ng / mL / hour to less than approximately 20 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 2 ng / mL / hour to less than approximately 19 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 3 ng / mL / hour to less than 18 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 4 ng / mL / hour to less than approximately 17 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 5 ng / mL / hour to less than approximately 16 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 6 ng / mL / hour to about 15 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of a muscarinic acetylcholine receptor inhibitor is approximately 7 ng / mL / hour to approximately 14 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of a muscarinic acetylcholine receptor inhibitor is approximately 8 ng / mL / hour to approximately 13 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of a muscarinic acetylcholine receptor inhibitor is approximately 9 ng / mL / hour to approximately 12 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of a muscarinic acetylcholine receptor inhibitor is approximately 10 ng / mL / hour to approximately 11 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of a muscarinic acetylcholine receptor inhibitor is approximately 1 ng / mL / hour to approximately 15 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of a muscarinic acetylcholine receptor inhibitor is approximately 2 ng / mL / hour to approximately 14 ng / mL / hour. In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 3 ng / mL / hour to approximately 13 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 4 ng / mL / hour to approximately 12 ng / mL / hour. In yet another embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 5 ng / mL / hour to approximately 11 ng / mL / hour.In one embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 6 ng / mL / hour to approximately 10 ng / mL / hour. In another embodiment, the rate of increase in serum concentration of muscarinic acetylcholine receptor inhibitors is approximately 7 ng / mL / hour to approximately 9 ng / mL / hour.

[0218] In one embodiment, the mean C serum concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 to approximately 1:50 over 24 hours after administration. In one embodiment, the mean C serum concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 to approximately 1:49 over 24 hours after administration. In one embodiment, the mean C serum concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 to approximately 1:48 over 24 hours after administration. In one embodiment, the mean C serum concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 to approximately 1:47 over 24 hours after administration. In one embodiment, the mean C serum concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to approximately 1:46 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 to approximately 1:45 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:11 to approximately 1:44 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:12 to approximately 1:43 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:13 to approximately 1:42 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 to approximately 1:41 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 to approximately 1:40 over 24 hours after administration. In another embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:39 over 24 hours after administration.In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:38 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:18 to approximately 1:37 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:19 to approximately 1:36 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:20 to approximately 1:35 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:21 to approximately 1:34 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:22 to approximately 1:33 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:23 to approximately 1:32 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:24 to approximately 1:31 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:25 to approximately 1:30 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:26 to approximately 1:29 over 24 hours after administration. In one embodiment, the mean serum C concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:27 to 1:28 over 24 hours after administration.

[0219] In one embodiment, (i) the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:1 to approximately 1:42, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 to approximately 1:50 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:2 to approximately 1:41, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 to approximately 1:4 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:3 to approximately 1:40 and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 to approximately 1:48 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:4 to approximately 1:39 and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 to approximately 1:47 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 to approximately 1:38, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to approximately 1:46 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 to approximately 1:37, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 to approximately 1:45 over 24 hours after administration.In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 to approximately 1:36, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:11 to approximately 1:44 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 to approximately 1:35, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:12 to approximately 1:43 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to approximately 1:33, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:13 to approximately 1:42 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 to approximately 1:32, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 to approximately 1:41 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:11 to approximately 1:31, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 to approximately 1:40 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:12 to approximately 1:29, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:39 over 24 hours after administration.In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:13 to approximately 1:28, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:38 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 to approximately 1:27, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:18 to approximately 1:37 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 to approximately 1:26, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:19 to approximately 1:36 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:25, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:20 to approximately 1:35 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:24, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:21 to approximately 1:34 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:18 to approximately 1:23, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:22 to approximately 1:33 over 24 hours after administration.In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:19 to approximately 1:22, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:23 to approximately 1:32 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:20 to approximately 1:21, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:24 to approximately 1:31 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 to approximately 1:21, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:25 to approximately 1:30 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:20, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:26 to approximately 1:29 over 24 hours after administration. In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:18, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:27 to approximately 1:28 over 24 hours after administration. In another embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:20, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 to approximately 1:11 over 24 hours after administration.In one embodiment, (i) the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:18, and (ii) the serum C(max) concentration ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to approximately 1:10 over 24 hours after administration.

[0220] In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:1 to approximately 1:20 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:2 to approximately 1:19 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:3 to approximately 1:18 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:4 to approximately 1:17 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 to approximately 1:16 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 to approximately 1:15 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 to approximately 1:14 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 to approximately 1:13 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to approximately 1:12 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 to approximately 1:11 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to 1:11 over 24 hours after administration.

[0221] In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:1 to approximately 1:38 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:2 to approximately 1:37 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:3 to approximately 1:36 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:4 to approximately 1:35 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 to approximately 1:34 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 to approximately 1:33 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 to approximately 1:32 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 to approximately 1:31 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 to approximately 1:30 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 to approximately 1:29 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:11 to approximately 1:28 over 24 hours after administration. In another embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:12 to approximately 1:27 over 24 hours after administration.In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:13 to approximately 1:26 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 to approximately 1:25 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 to approximately 1:24 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:23 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:22 over 24 hours post-administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:18 to approximately 1:21 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 to approximately 1:22 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 to approximately 1:21 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 to approximately 1:20 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to approximately 1:19 over 24 hours after administration. In one embodiment, the serum area under the curve (AUC) ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 to 1:20 over 24 hours after administration.

[0222] In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:1 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:2 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:3 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:4 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:11 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:12 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:13 over 24 hours after administration. In another embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 over 24 hours after administration.In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:18 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:19 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:20 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:21 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:22 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:23 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:24 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:25 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:26 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:27 over 24 hours after administration. In another embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:28 over 24 hours after administration.In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:29 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:30 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:31 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:31 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:32 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:33 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:34 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:35 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:36 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:37 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:38 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:39 over 24 hours after administration. In one embodiment, the serum AUC ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:40 over 24 hours after administration.

[0223] In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:1 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:2 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:3 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:4 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:5 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:6 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:7 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:8 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:9 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:10 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:11 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:12 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:13 over 24 hours after administration.In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:14 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:15 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:16 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:17 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:18 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:19 over 24 hours after administration. In one embodiment, the C(max) serum ratio of muscarinic acetylcholine receptor inhibitors to muscarinic receptor activators is approximately 1:20 over 24 hours after administration.

[0224] In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:28 ng / mL to approximately 1:32 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i) racemic THP to (ii) racemic BTC is approximately 1:29 ng / mL to approximately 1:31 ng / mL after administration. In one embodiment, the plasma concentration ratio was determined approximately 30 minutes to 24 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 1 hour to 22 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 2 hours to 20 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 3 hours to 17 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 4 hours to 15 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 5 hours to 12 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 6 hours to 10 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 7 hours to 9 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the plasma concentration ratio was determined approximately 1 hour after administration.In one embodiment, the plasma concentration ratio was determined approximately 2 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 3 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 4 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 5 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 6 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 7 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 8 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 9 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 10 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 11 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 12 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 13 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 14 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 15 hours after administration. In one embodiment, the plasma concentration ratio was determined approximately 16 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 17 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 18 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 19 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 20 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 21 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 22 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 23 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 24 hours after administration.

[0225] In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:20 ng / mL to approximately 1:40 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:21 ng / mL to approximately 1:39 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:22 ng / mL to approximately 1:38 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:23 ng / mL to approximately 1:37 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:24 ng / mL to approximately 1:36 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:25 ng / mL to approximately 1:35 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:26 ng / mL to approximately 1:34 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:27 ng / mL to approximately 1:33 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:28 ng / mL to approximately 1:32 ng / mL after administration. In one embodiment, the plasma concentration ratio of (i)(R)-THP to (ii)-racemic BTC is approximately 1:29 ng / mL to approximately 1:31 ng / mL after administration. In one embodiment, the plasma concentration ratio was determined approximately 30 minutes to 24 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 1 hour to 22 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 2 hours to 20 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 3 hours to 17 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 4 hours to 15 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 5 hours to 12 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 6 hours to 10 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 7 hours to 9 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 30 minutes after administration. In another embodiment, the plasma concentration ratio was determined approximately 1 hour after administration.In one embodiment, the plasma concentration ratio was determined approximately 2 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 3 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 4 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 5 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 6 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 7 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 8 hours after administration. In another embodiment, the plasma concentration ratio was determined approximately 9 hours after administration. In another embodiment, the plasma ...

Claims

1. A method for treating a motor disorder in a patient, comprising administering to a patient in need of such treatment (i) an amount effective for treating the motor disorder and (ii) an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, thereby treating the motor disorder.

2. The method according to claim 1, wherein a muscarinic acetylcholine receptor inhibitor is distributed to the central and peripheral nervous systems of a patient.

3. The method according to claim 1 or 2, wherein the muscarinic acetylcholine receptor activator is distributed primarily to the peripheral nervous system of the patient.

4. The method according to claim 1 or 2, wherein the molar ratio of (i) a muscarinic acetylcholine receptor activator present in the patient's peripheral nervous system to (ii) a muscarinic acetylcholine receptor activator present in the patient's central nervous system is at least 5 to 1.

5. The method according to claim 1 or 2, wherein the molar ratio of (i) a muscarinic acetylcholine receptor activator present in the patient's peripheral nervous system to (ii) a muscarinic acetylcholine receptor activator present in the patient's central nervous system is at least 10 to 1.

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

7. The method according to any one of claims 1 to 5, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

8. The method according to any one of claims 1 to 5, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having stereochemical purity with at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof.

9. The method according to any one of claims 1 to 5, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having stereochemical purity with at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof.

10. A method for treating a motor disorder in a patient, comprising administering to a patient in need (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having a stereochemical purity of at least 95% enantiomer excess, and (ii) a muscarinic acetylcholine receptor activator, thereby treating the motor disorder.

11. The method of claim 10, wherein a muscarinic acetylcholine receptor activator is administered to the patient in an amount effective in reducing the side effects of a muscarinic acetylcholine receptor inhibitor.

12. The method according to any one of claims 1 to 11, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

13. The method according to any one of claims 1 to 11, wherein the muscarinic acetylcholine receptor activator is racemic betanethyl or a pharmaceutically acceptable salt thereof.

14. The method according to any one of claims 1 to 11, wherein the muscarinic acetylcholine receptor activator is (S)-bethanechol having stereochemical purity with at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof.

15. The method according to any one of claims 1 to 11, wherein the muscarinic acetylcholine receptor activator is (S)-bethanechol having stereochemical purity with at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof.

16. The method according to any one of claims 1 to 11, wherein (a) the muscarinic acetylcholine receptor activator is racemic betanethyl or a pharmaceutically acceptable salt thereof, and (b) the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 96% enantiomer excess, or a pharmaceutically acceptable salt thereof.

17. The method according to any one of claims 1 to 16, wherein a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator are administered simultaneously to the patient.

18. The method according to any one of claims 1 to 16, wherein a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator are each present in a single pharmaceutical composition administered to a patient.

19. The method of claim 18, wherein the pharmaceutical composition is in the form of a tablet, lozenge, liquid, droplet, capsule, caplet, gel cap, sublingual formulation, or spray.

20. The method of claim 18, wherein the pharmaceutical composition is in the form of a tablet, lozenge, capsule, caplet, or gel cap.

21. The method according to any one of claims 18 to 20, wherein the pharmaceutical composition is a controlled-release formulation.

22. The method according to any one of claims 18 to 20, wherein the pharmaceutical composition comprises (i) a controlled-release component containing a muscarinic acetylcholine receptor inhibitor and (ii) an immediate-release component containing a muscarinic acetylcholine receptor activator.

23. The method according to any one of claims 18 to 20, wherein the pharmaceutical composition comprises (i) a controlled-release component containing a muscarinic acetylcholine receptor activator and (ii) an immediate-release component containing a muscarinic acetylcholine receptor inhibitor.

24. The method according to any one of claims 18 to 23, wherein the pharmaceutical composition is administered orally to a patient.

25. The method according to any one of claims 18 to 24, wherein the pharmaceutical composition is administered daily.

26. The method according to any one of claims 18 to 24, wherein the pharmaceutical composition is administered twice a day.

27. The method according to any one of claims 18 to 24, wherein the pharmaceutical composition is administered three times a day.

28. The method according to any one of claims 1 to 27, wherein a muscarinic acetylcholine receptor inhibitor is administered orally in the absence of a muscarinic acetylcholine receptor activator in a dose that causes at least one adverse side effect selected from dry mouth, dry eyes, blurred vision, tachycardia, confusion, amnesia, hallucinations, constipation, and urinary retention.

29. The method according to any one of claims 1 to 28, wherein a muscarinic acetylcholine receptor inhibitor is administered orally at an initial dose of more than 10 mg / day.

30. A method according to any one of claims 1 to 29, wherein a muscarinic acetylcholine receptor inhibitor is administered orally in a dose ranging from approximately 10 mg to approximately 1000 mg.

31. The method according to any one of claims 1 to 30, wherein a muscarinic acetylcholine receptor activator is administered orally in a dose ranging from approximately 50 mg to approximately 1000 mg.

32. The method according to any one of claims 1 to 31, wherein the motor disorder is dystonia.

33. The method according to any one of claims 1 to 31, wherein the motor impairment is primary dystonia, secondary dystonia, tardive dystonia, drug-induced dystonia, or cerebral palsy-related dystonia.

34. The method according to any one of claims 1 to 31, wherein the motor impairment is focal dystonia.

35. The method of claim 34, wherein the focal dystonia is cervical dystonia, blepharospasm, hand dystonia, writer's cramp, musician's dystonia, lower limb dystonia, or foot dystonia.

36. The method according to any one of claims 1 to 31, wherein the motor disorder is segmental dystonia, unilateral dystonia, multifocal dystonia, or generalized dystonia.

37. A method according to any one of claims 1 to 36, wherein the motor disorder is of idiopathic origin.

38. The method according to any one of claims 1 to 31, wherein the motor disorder is hereditary dystonia.

39. Hereditary dystonia is associated with mutations in one or more genes selected from TOR1A, THAP1, ANO3, GNAL, KMT2B, GCH1, SPR, TAF1, PRKRA, ATP1A3, SGCE, PNKD, PRRT2, SLC2A1, and ECHS1. The method of claim 38.

40. The method according to any one of claims 1 to 31, wherein the motor impairment is multiple system atrophy, progressive supranuclear palsy, or tremor.

41. The method according to any one of claims 1 to 31, wherein the motor impairment is Parkinson's disease, drug-induced Parkinson's disease, Huntington's disease, or Lewy body dementia.

42. A method according to any one of claims 1 to 41, wherein the patient experiences dizziness at an incidence rate of less than four times per week while receiving a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

43. A method according to any one of claims 1 to 42, wherein a patient experiences dizziness with an incidence of fewer than four times per week while receiving a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

44. A method according to any one of claims 1 to 43, wherein a patient experiences headaches with an incidence of fewer than three times per week while receiving a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

45. A method according to any one of claims 1 to 44, wherein a patient experiences nausea with an incidence of fewer than three times per week while receiving a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator.

46. A method according to any one of claims 1 to 45, wherein the patient experiences an adverse side effect selected from vomiting, diarrhea, salivation, and eating disorder with an incidence of fewer than five times per week.

47. The method according to any one of claims 1 to 46, wherein the patient is an adult.

48. The method according to any one of claims 1 to 46, wherein the patient is a child.

49. A method for treating a motor disorder in a patient, comprising administering to a patient in need (i) an amount effective for treating the motor disorder and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, thereby treating the motor disorder, wherein the second therapeutic agent is administered to the patient in an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

50. The method according to claim 49, wherein a muscarinic acetylcholine receptor inhibitor is distributed to the central and peripheral nervous systems of a patient.

51. The method of claim 49 or 50, wherein a muscarinic acetylcholine receptor activator is distributed primarily to the peripheral nervous system of the patient.

52. The method according to any one of claims 49 to 51, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

53. The method according to any one of claims 49 to 51, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

54. The method according to any one of claims 49 to 53, wherein the second therapeutic agent is a cholinergic promoter.

55. The method according to any one of claims 49 to 53, wherein the second therapeutic agent is an acetylcholinesterase inhibitor.

56. The method according to any one of claims 49 to 53, wherein the second therapeutic agent is pyridostigmine, neostigmine, physostigmine, edrophonium, or a pharmaceutically acceptable salt thereof.

57. The method according to any one of claims 49 to 53, wherein the second therapeutic agent is distigmine bromide.

58. The method according to any one of claims 49 to 57, wherein the patient does not experience any adverse side effects from the second therapeutic agent.

59. A method according to any one of claims 1 to 53, wherein the patient does not experience any adverse side effects from the muscarinic acetylcholine receptor activator.

60. A method according to any one of claims 1 to 59, wherein the patient does not experience any adverse side effects from the muscarinic acetylcholine receptor inhibitor.

61. A method according to any one of claims 1 to 60, wherein while a patient is receiving a muscarinic acetylcholine receptor inhibitor and a muscarinic acetylcholine receptor activator, the patient experiences (a) dizziness, lightheadedness, headache, and / or nausea with an incidence of less than five times per week; (b) vomiting, diarrhea, salivation, and eating disorders with an incidence of less than five times per week; or both (a) and (b).

62. An oral pharmaceutical composition comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) an amount effective in reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, and (iii) a pharmaceutically acceptable carrier.

63. The pharmaceutical composition according to claim 62, wherein a muscarinic acetylcholine receptor inhibitor is distributed to the central and peripheral nervous systems of a patient.

64. The pharmaceutical composition of claim 62 or 63, wherein the muscarinic acetylcholine receptor activator is mainly distributed to the peripheral nervous system of the patient.

65. The pharmaceutical composition according to claim 62 or 63, wherein, upon oral administration of the pharmaceutical composition to a human patient, the molar ratio of (i) a muscarinic acetylcholine receptor activator present in the patient's peripheral nervous system to (ii) a muscarinic acetylcholine receptor activator present in the patient's central nervous system is at least 5 to 1.

66. The pharmaceutical composition according to claim 62 or 63, wherein, upon oral administration of the pharmaceutical composition to a human patient, the molar ratio of (i) a muscarinic acetylcholine receptor activator present in the patient's peripheral nervous system to (ii) a muscarinic acetylcholine receptor activator present in the patient's central nervous system is at least 10 to 1.

67. A pharmaceutical composition according to any one of claims 62 to 66, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

68. A pharmaceutical composition according to any one of claims 62 to 66, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

69. A pharmaceutical composition according to any one of claims 62 to 66, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having stereochemical purity with at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof.

70. A pharmaceutical composition according to any one of claims 62 to 66, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having stereochemical purity with at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof.

71. A pharmaceutical composition comprising (i) a muscarinic acetylcholine receptor inhibitor selected from (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess, (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier.

72. The pharmaceutical composition according to claim 71, wherein a muscarinic acetylcholine receptor activator is present in an amount effective in reducing the side effects of a muscarinic acetylcholine receptor inhibitor.

73. The pharmaceutical composition according to claim 71 or 72, wherein the pharmaceutical composition is formulated for oral administration.

74. A pharmaceutical composition according to any one of claims 62 to 73, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

75. A pharmaceutical composition according to any one of claims 62 to 73, wherein the muscarinic acetylcholine receptor activator is racemic betanethyl or a pharmaceutically acceptable salt thereof.

76. A pharmaceutical composition according to any one of claims 62 to 73, wherein the muscarinic acetylcholine receptor activator is (S)-bethanechol having a stereochemical purity of at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof.

77. A pharmaceutical composition according to any one of claims 62 to 73, wherein the muscarinic acetylcholine receptor activator is (S)-bethanechol having a stereochemical purity of at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof.

78. A pharmaceutical composition according to any one of claims 62 to 73, wherein (a) the muscarinic acetylcholine receptor activator is racemic betanethyl or a pharmaceutically acceptable salt thereof, and (b) the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having a stereochemical purity of at least 96% enantiomer excess, or a pharmaceutically acceptable salt thereof.

79. An oral pharmaceutical composition comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, and (iii) a pharmaceutically acceptable carrier, wherein the second therapeutic agent is present in an amount effective in reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

80. The pharmaceutical composition according to claim 79, wherein a muscarinic acetylcholine receptor inhibitor is distributed to the central and peripheral nervous systems of a patient.

81. The pharmaceutical composition of claim 79 or 80, wherein the muscarinic acetylcholine receptor activator is mainly distributed to the peripheral nervous system of the patient.

82. A pharmaceutical composition according to any one of claims 79 to 81, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

83. A pharmaceutical composition according to any one of claims 79 to 82, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

84. A pharmaceutical composition according to any one of claims 79 to 83, wherein the second treatment is a cholinergic stimulant.

85. A pharmaceutical composition according to any one of claims 79 to 83, wherein the second treatment is an acetylcholinesterase inhibitor.

86. A pharmaceutical composition according to any one of claims 79 to 83, wherein the second therapeutic agent is pyridostigmine, neostigmine, physostigmine, edrophonium, or a pharmaceutically acceptable salt thereof.

87. A pharmaceutical composition according to any one of claims 79 to 83, wherein the second treatment is distigmine bromide.

88. An oral pharmaceutical composition comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier.

89. The pharmaceutical composition of claim 88, wherein a muscarinic acetylcholine receptor inhibitor is distributed to the central and peripheral nervous systems of a patient.

90. The pharmaceutical composition according to claim 88 or 89, wherein the muscarinic acetylcholine receptor activator is mainly distributed to the peripheral nervous system of the patient.

91. The pharmaceutical composition according to claim 88 or 89, wherein, upon oral administration of the pharmaceutical composition to a human patient, the molar ratio of (i) a muscarinic acetylcholine receptor activator present in the patient's peripheral nervous system to (ii) a muscarinic acetylcholine receptor activator present in the patient's central nervous system is at least 5 to 1.

92. The pharmaceutical composition according to claim 88 or 89, wherein, upon oral administration of the pharmaceutical composition to a human patient, the molar ratio of (i) a muscarinic acetylcholine receptor activator present in the patient's peripheral nervous system to (ii) a muscarinic acetylcholine receptor activator present in the patient's central nervous system is at least 10 to 1.

93. A pharmaceutical composition according to any one of claims 88 to 92, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

94. A pharmaceutical composition according to any one of claims 88 to 92, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

95. A pharmaceutical composition according to any one of claims 88 to 92, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having stereochemical purity with at least 95% enantiomer excess, or a pharmaceutically acceptable salt thereof.

96. A pharmaceutical composition according to any one of claims 88 to 92, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl having stereochemical purity with at least 98% enantiomer excess, or a pharmaceutically acceptable salt thereof.

97. An oral pharmaceutical composition comprising (i) a muscarinic acetylcholine receptor inhibitor, (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, and (iii) a pharmaceutically acceptable carrier.

98. The pharmaceutical composition according to claim 97, wherein a muscarinic acetylcholine receptor inhibitor is distributed to the central and peripheral nervous systems of a patient.

99. The pharmaceutical composition according to claim 97 or 98, wherein the muscarinic acetylcholine receptor activator is mainly distributed to the peripheral nervous system of the patient.

100. A pharmaceutical composition according to any one of claims 97 to 99, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

101. A pharmaceutical composition according to any one of claims 97 to 100, wherein the muscarinic acetylcholine receptor inhibitor is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

102. A pharmaceutical composition according to any one of claims 97 to 101, wherein the second treatment is a cholinergic promoter.

103. A pharmaceutical composition according to any one of claims 97 to 101, wherein the second treatment is an acetylcholinesterase inhibitor.

104. A pharmaceutical composition according to any one of claims 97 to 101, wherein the second therapeutic agent is pyridostigmine, neostigmine, physostigmine, edrophonium, or a pharmaceutically acceptable salt thereof.

105. A pharmaceutical composition according to any one of claims 97 to 101, wherein the second treatment is distigmine bromide.

106. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a tablet, lozenge, liquid, droplet, capsule, caplet, gel cap, sublingual preparation, or spray.

107. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a tablet, lozenge, capsule, caplet, or gel cap.

108. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a tablet.

109. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a lozenge.

110. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a capsule.

111. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a caplet.

112. A pharmaceutical composition according to any one of claims 62 to 105, wherein the pharmaceutical composition is in the form of a gel cap.

113. A pharmaceutical composition according to any one of claims 62 to 112, wherein the pharmaceutical composition is a controlled-release formulation.

114. A pharmaceutical composition according to any one of claims 62 to 113, wherein the pharmaceutical composition comprises (i) a controlled-release component containing a muscarinic acetylcholine receptor inhibitor and (ii) an immediate-release component containing a muscarinic acetylcholine receptor activator.

115. An oral pharmaceutical composition comprising (i) an effective amount of a muscarinic acetylcholine receptor inhibitor for the treatment of a motor disorder, (ii) an effective amount of a muscarinic acetylcholine receptor activator for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor, and (iii) a pharmaceutically acceptable carrier.

116. The oral pharmaceutical composition according to claim 115, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

117. The oral pharmaceutical composition of claim 116, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof.

118. The oral pharmaceutical composition of claim 116, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

119. The oral pharmaceutical composition of claim 118, wherein (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess.

120. The oral pharmaceutical composition of claim 116, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof, betanethol is racemic betanethol or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethol are administered in a weight ratio of more than 1:1 trihexyphenidyl to betanethol.

121. An oral pharmaceutical composition according to claim 120, wherein the weight ratio of trihexyphenidyl to betanethyl is about 1:1.1 to about 1:

10.

122. The oral pharmaceutical composition of claim 116, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of (R)-trihexyphenidyl to betanethyl greater than 1:

1.

123. The oral pharmaceutical composition according to claim 122, wherein the weight ratio of (R)-trihexyphenidyl to betanethyl is about 1:1.1 to about 1:

20.

124. An oral pharmaceutical composition according to any one of claims 115 to 123, wherein the oral pharmaceutical composition is a controlled-release formulation.

125. An oral pharmaceutical composition according to any one of claims 115 to 124, wherein the oral pharmaceutical composition is administered once a day.

126. An oral pharmaceutical composition according to any one of claims 115 to 124, wherein the oral pharmaceutical composition is administered twice a day.

127. An oral pharmaceutical composition comprising (i) an effective amount of a muscarinic acetylcholine receptor inhibitor for the treatment of a motor disorder, (ii) a muscarinic acetylcholine receptor activator, and (iii) a pharmaceutically acceptable carrier, wherein, when administered to a patient in need, the composition is sufficient to provide an in vivo plasma profile, wherein the rate of increase of the plasma concentration of the muscarinic acetylcholine receptor inhibitor is less than approximately 15 ng / mL / hour.

128. The oral pharmaceutical composition according to claim 127, wherein the oral pharmaceutical composition is a controlled-release formulation.

129. An oral pharmaceutical composition according to claim 127 or 128, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

130. The oral pharmaceutical composition according to claim 129, wherein trihexyphenidyl or a pharmaceutically acceptable salt thereof is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

131. The oral pharmaceutical composition of claim 130, wherein (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess.

132. An oral pharmaceutical composition according to any one of claims 127 to 131, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

133. An oral pharmaceutical composition according to any one of claims 127 to 131, wherein the intensity or severity of at least one of the side effects of a muscarinic acetylcholine receptor inhibitor is reduced in a subject compared to a subject administered an immediate-release formulation of a muscarinic acetylcholine receptor inhibitor alone.

134. An oral pharmaceutical composition according to any one of claims 127 to 133, wherein the mean plasma concentration ratio of a muscarinic acetylcholine receptor inhibitor to a muscarinic receptor activator is approximately 1:5 to approximately 1:50 over 24 hours after administration.

135. A pharmaceutical composition according to any one of claims 127 to 134, wherein the oral pharmaceutical composition is administered once a day.

136. A pharmaceutical composition according to any one of claims 127 to 134, wherein the oral pharmaceutical composition is administered twice a day.

137. A unit-dose formulation comprising any of the pharmaceutical compositions of claims 62 to 136.

138. A unit dose formulation according to claim 137, wherein the unit dose formulation contains approximately 10 mg to approximately 1000 mg of a muscarinic acetylcholine receptor inhibitor.

139. A unit dose formulation according to claim 137 or 138, wherein the unit dose formulation comprises approximately 50 mg to approximately 1000 mg of a muscarinic acetylcholine receptor activator.

140. A method for treating a motor disorder in a subject requiring treatment, comprising administering to the subject (i) an amount effective for treating the motor disorder of a muscarinic acetylcholine receptor inhibitor and (ii) an amount effective for reducing the frequency and / or intensity of at least one adverse event of the muscarinic acetylcholine receptor inhibitor, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

141. The method of claim 140, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof.

142. The method of claim 141, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

143. The method of claim 142, wherein (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess.

144. A method, according to claim 140, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof, and betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of about 1:1.1 to about 1:

10.

145. A method, according to claim 140, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, betanecole is racemic betanecole or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanecole are administered in a weight ratio of about 1:1.1 to about 1:

20.

146. The method according to any one of claims 140 to 145, wherein the mean plasma concentration ratio of a muscarinic acetylcholine receptor inhibitor to a muscarinic receptor activator is approximately 1:5 to approximately 1:50 over 24 hours after administration.

147. The method of any one of claims 140 to 146, wherein the motor disorder is selected from the group consisting of dystonia, primary dystonia, secondary dystonia, multifocal dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-related dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer's cramp, musician's dystonia, lower limb dystonia, foot dystonia, segmental dystonia, generalized dystonia, hereditary dystonia, multiple system atrophy, progressive supranuclear palsy, tremor, Parkinson's disease, drug-induced Parkinson's disease, Huntington's disease, and Lewy body dementia.

148. The method according to any one of claims 140 to 147, wherein the side effects are selected from the group consisting of dry mouth, dry eyes, blurred vision, tachycardia, constipation, urinary retention, visual impairment, constipation, nausea, muscle spasms, decreased urination, skin flushing, fever, decreased sweating, and cardiac arrhythmia.

149. (i) Effective doses of muscarinic acetylcholine receptor inhibitors for the treatment of motor disorders, (ii) an amount of muscarinic acetylcholine receptor activator effective in reducing the frequency of at least one of the side effects of a muscarinic acetylcholine receptor inhibitor, and (iii) A pharmaceutically acceptable carrier Includes, Here, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, The muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof. Oral pharmaceutical composition.

150. The oral pharmaceutical composition of claim 149, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof.

151. The oral pharmaceutical composition according to claim 149, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

152. The oral pharmaceutical composition of claim 151, wherein (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess.

153. The oral pharmaceutical composition of claim 149, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof, and betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of more than 1:1 trihexyphenidyl to betanethyl.

154. The oral pharmaceutical composition according to claim 153, wherein the weight ratio of trihexyphenidyl to betanethyl is about 1:1.1 to about 1:

10.

155. The oral pharmaceutical composition of claim 149, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of (R)-trihexyphenidyl to betanethyl greater than 1:

1.

156. The oral pharmaceutical composition according to claim 155, wherein the weight ratio of (R)-trihexyphenidyl to betanethyl is about 1:1.1 to about 1:

20.

157. The oral pharmaceutical composition according to claim 149, wherein the oral pharmaceutical composition is a controlled-release formulation.

158. The pharmaceutical composition according to claim 149, wherein the oral pharmaceutical composition is administered once a day.

159. The pharmaceutical composition according to claim 149, wherein the oral pharmaceutical composition is administered twice a day.

160. A method for treating motor impairment in a subject requiring treatment, wherein the subject: (i) an effective amount of a muscarinic acetylcholine receptor inhibitor for treating motor disorders, and (ii) an amount of muscarinic acetylcholine receptor activator effective in reducing the frequency of at least one of the side effects of a muscarinic acetylcholine receptor inhibitor. This includes administering, Here, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, The muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof. method.

161. The method of claim 160, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof.

162. The method of claim 160, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof.

163. The method of claim 162, wherein (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof has a stereochemical purity of at least 95% enantiomer excess.

164. A method, according to claim 160, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof, and betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of about 1:1.1 to about 1:

10.

165. A method of administering trihexyphenidyl, wherein (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, where bethanechol is racemic bethanechol or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and bethanechol are administered in a weight ratio of about 1:1.1 to about 1:20, the method of claim 160.

166. The method of claim 160, wherein the mean plasma concentration ratio of a muscarinic acetylcholine receptor inhibitor to a muscarinic receptor activator is approximately 1:5 to approximately 1:50 over 24 hours after administration.

167. The method of claim 160, wherein the motor disorder is selected from the group consisting of dystonia, primary dystonia, secondary dystonia, multifocal dystonia, tardive dystonia, drug-induced dystonia, cerebral palsy-related dystonia, focal dystonia, cervical dystonia, blepharospasm, hand dystonia, writer's cramp, musician's dystonia, lower limb dystonia, foot dystonia, segmental dystonia, generalized dystonia, hereditary dystonia, multiple system atrophy, progressive supranuclear palsy, tremor, Parkinson's disease, drug-induced Parkinson's disease, Huntington's disease, or Lewy body dementia.

168. The method of claim 160, wherein the side effects are selected from the group consisting of dry mouth, dry eyes, blurred vision, tachycardia, constipation, urinary retention, visual impairment, constipation, nausea, muscle spasms, decreased urination, skin flushing, fever, decreased sweating, cardiac arrhythmia, and combinations thereof.

169. (i) Effective doses of muscarinic acetylcholine receptor inhibitors for the treatment of motor disorders (ii) an amount of muscarinic acetylcholine receptor activator effective in reducing the frequency of at least one of the side effects of a muscarinic acetylcholine receptor inhibitor, and (iii) A pharmaceutically acceptable carrier An oral pharmaceutical composition comprising, Here, when the composition is administered to a subject requiring it, it is sufficient to provide an in vivo plasma profile of a muscarinic acetylcholine receptor inhibitor. Here, the rate of increase in plasma concentration of muscarinic acetylcholine receptor inhibitors is less than approximately 15 ng / mL / hour. The muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, where the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof, and It is a controlled-release formulation. Oral pharmaceutical composition.

170. The oral pharmaceutical composition of claim 169, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof.

171. The oral pharmaceutical composition of claim 169, wherein the trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess.

172. The oral pharmaceutical composition of claim 169, wherein the intensity or severity of at least one of the side effects of trihexyphenidyl or a pharmaceutically acceptable salt thereof is reduced in a subject compared to a subject administered an immediate-release formulation of trihexyphenidyl or a pharmaceutically acceptable salt thereof alone.

173. The oral pharmaceutical composition according to claim 169, wherein the C (mean) plasma concentration ratio of trihexyphenidyl or a pharmaceutically acceptable salt thereof to bethanechol or a pharmaceutically acceptable salt thereof is about 1:5 to about 1:50 over 24 hours after administration.

174. A method for treating motor impairment in a subject requiring treatment, wherein the subject: (i) an effective amount of a muscarinic acetylcholine receptor inhibitor for treating motor disorders, and (ii) an amount of muscarinic acetylcholine receptor activator effective in reducing the frequency of at least one of the side effects of a muscarinic acetylcholine receptor inhibitor. This includes administering, Here, muscarinic acetylcholine receptor inhibitors have an in vivo plasma profile with an increase rate of less than approximately 15 ng / mL / hour in the target population. Here, the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof, and the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof. method.

175. The method of claim 174, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof.

176. The method of claim 174, wherein the trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof having stereochemical purity with at least 95% enantiomer excess.

177. A method, according to claim 174, wherein trihexyphenidyl is racemic trihexyphenidyl or a pharmaceutically acceptable salt thereof, and betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of about 1:1.1 to about 1:

10.

178. A method, according to claim 174, wherein trihexyphenidyl is (R)-trihexyphenidyl or a pharmaceutically acceptable salt thereof, betanethyl is racemic betanethyl or a pharmaceutically acceptable salt thereof, and trihexyphenidyl and betanethyl are administered in a weight ratio of about 1:1.1 to about 1:

20.

179. For the manufacture of a pharmaceutical product for the treatment of motor disorders in patients, the use of (i) an amount effective for the treatment of motor disorders, a muscarinic acetylcholine receptor inhibitor, and (ii) an amount effective for reducing the frequency and / or intensity of at least one side effect of the muscarinic acetylcholine receptor inhibitor.

180. The use of claim 179, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

181. The use of claim 179 or 180, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

182. Use of any of claims 179 to 181, wherein the motor disorder is dystonia.

183. Use for the manufacture of a medicament for the treatment of movement disorders in patients, wherein (i) an amount effective for the treatment of movement disorders is a muscarinic acetylcholine receptor inhibitor and (ii) a second therapeutic agent selected from muscarinic acetylcholine receptor activators, cholinergic promoters, and acetylcholinesterase inhibitors, wherein the second therapeutic agent is administered to the patient in an amount effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor.

184. A pharmaceutical composition for use in treating a motor disorder in a subject, comprising (i) an amount effective for treating the motor disorder, a muscarinic acetylcholine receptor inhibitor, and (ii) an amount effective for reducing the frequency and / or intensity of the motor disorder, a muscarinic acetylcholine receptor activator.

185. The pharmaceutical composition of claim 184, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

186. The pharmaceutical composition of claim 184 or 185, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

187. A pharmaceutical composition according to any one of claims 184 to 186, wherein the movement disorder is dystonia.

188. A combination agent for use in the treatment of motor disorders in subjects, comprising (i) an amount effective for treating motor disorders, and (ii) an amount effective for reducing the frequency and / or intensity of motor disorders, comprising a muscarinic acetylcholine receptor inhibitor.

189. The combination agent of claim 188, wherein the muscarinic acetylcholine receptor inhibitor is trihexyphenidyl or a pharmaceutically acceptable salt thereof.

190. The combination agent of claim 188 or 189, wherein the muscarinic acetylcholine receptor activator is bethanechol or a pharmaceutically acceptable salt thereof.

191. A combination agent according to any one of claims 188 to 190, wherein the motor disorder is dystonia.

192. A muscarinic acetylcholine receptor inhibitor for use in a method for treating a movement disorder in a patient, wherein the method comprises administering to a patient in need (i) an amount of the muscarinic acetylcholine receptor inhibitor effective for treating the movement disorder and (ii) an amount of a muscarinic acetylcholine receptor activator effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, thereby treating the movement disorder.

193. A muscarinic acetylcholine receptor inhibitor according to claim 192, for use in the treatment of dystonia.

194. A muscarinic acetylcholine receptor activator for use in a method for treating a movement disorder in a patient, wherein the method comprises administering to a patient in need (i) an amount effective for treating the movement disorder and (ii) an amount of the muscarinic acetylcholine receptor activator effective for reducing the frequency and / or intensity of at least one of the side effects of the muscarinic acetylcholine receptor inhibitor, thereby treating the movement disorder.

195. A muscarinic acetylcholine receptor activator according to claim 194, for use in the treatment of dystonia.

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