Methods of treating symptoms of autism spectrum disorders

Abstract

Provided herein are methods of treating symptoms associated with autism spectrum disorder (ASD) by administering a therapeutically effective amount of a triptan.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Application Serial No. 62 / 925,023, filed October 23, 2019, and U.S. Provisional Application Serial No. 63 / 011,715, filed April 17, 2020, the contents of which are incorporated herein by reference in their entirety for all purposes. Background Technology

[0003] Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by stereotyped behaviors and deficits in language and social interaction. As of 2014, the reported incidence of autism in the United States had rapidly risen to 1 in 59 newborns (https: / / www.cdc.gov / mmwr / volumes / 67 / ss / ss6706a1.htm), representing a significant medical and social burden for decades to come. To date, there are no FDA-approved treatments for reducing or eliminating the core symptoms of autism spectrum disorder. There is a need in the art for methods to treat symptoms associated with autism spectrum disorder and to reduce their severity and incidence, including increased irritability and reduced social skills. Summary of the Invention

[0004] In some implementations, this disclosure provides a method for treating symptoms associated with autism spectrum disorder (ASD), the method comprising administering a therapeutically effective amount of a triptan to a patient in need.

[0005] In some embodiments, this disclosure provides a method for treating symptoms associated with ASD, the method comprising administering to a patient in need a therapeutically effective amount of zolmitriptan or a pharmaceutically acceptable salt thereof.

[0006] In some embodiments, this disclosure provides a method for treating symptoms associated with ASD, the method comprising administering to a patient in need a therapeutically effective amount of sumatriptan or a pharmaceutically acceptable salt thereof.

[0007] In some embodiments, this disclosure provides a method for treating symptoms associated with ASD, the method comprising administering a therapeutically effective amount of a triptan to a patient in need, wherein the patient experiences a significant improvement in social competence after treatment compared to before treatment.

[0008] In some embodiments, this disclosure provides a method for treating symptoms associated with ASD, the method comprising administering a therapeutically effective amount of a triptan to a patient in need, wherein, after treatment, the patient experiences a significant reduction in ASD-related irritability compared to before treatment. In some embodiments, this disclosure provides a method for treating aggression associated with autism spectrum disorder (ASD), the method comprising administering a therapeutically effective amount of a triptan to a patient in need, wherein, after treatment, the patient experiences a significant reduction in ASD-related aggression compared to before treatment. Attached Figure Description

[0009] Figure 1 shows the attack frequency in BALB / c resident mouse cages from the cross-resident-intruder (RI) study, in which resident BALB / c mice were treated with a mediator control followed by treatment with 3 mg / kg or 10 mg / kg zolmitriptan.

[0010] Figure 2 shows the attack time (in seconds) in cages of BALB / c resident mice from a cross-resident-invader (RI) study, where resident BALB / c mice were treated with a mediator control followed by treatment with 3 mg / kg or 10 mg / kg zolmitriptan.

[0011] Figure 3 shows the attack time (in seconds) in adult male CD-1 mice from a cross-resident-invader (RI) study, where resident CD-1 mice were treated with a mediator control, 10 mg / kg zolmitriptan, or 0.03 mg / kg risperidone. As a crossover design, attack time was measured over a 5-minute time interval. Data are expressed as mean ± standard error of the mean.

[0012] Figure 4 shows the social competence index in a c57 / Bl6 mouse model of autism spectrum disorder induced by valproic acid (VPA) in mice treated with a mediator control or 10 mg / kg zolmitriptan.

[0013] Figure 5 shows the mean CSF levels of zolmitriptan and its metabolite N-desmethylzolmitriptan (NDMZ) after oral administration of 5 mg, 10 mg, 20 mg and 30 mg doses to human subjects.

[0014] definition

[0015] Throughout this disclosure, numerous patents, patent applications, and publications (including non-patent publications) are referenced. The disclosures of these patents, patent applications, and publications are incorporated herein by reference, in their entirety, for all purposes, to provide a more comprehensive description of the prior art known to those skilled in the art as of the date of this disclosure. In the event of any inconsistency between the referenced patents, patent applications, and publications and this disclosure, this disclosure shall prevail.

[0016] For convenience, certain terms used in the specification, embodiments, and claims are collected herein. Unless otherwise defined, all technical and scientific terms used in this disclosure have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0017] The term “about” when immediately preceding a numerical value indicates a range (e.g., plus or minus 10% of that value). For example, “about 50” can mean 45 to 55, and “about 25,000” can mean 22,500 to 27,500, etc., unless the context of this disclosure indicates otherwise, or the context is inconsistent with such interpretation. For example, in a list of numerical values ​​such as “about 49, about 50, about 55, …”, “about 50” means a range less than half of one or more intervals between the preceding and following values, such as greater than 49.5 to less than 52.5. Furthermore, the phrases “less than about” or “greater than about” should be understood in light of the definition of the term “about” provided herein. Similarly, the term “about” when preceding a series of numerical values ​​or a range of values ​​(e.g., “about 10, 20, 30” or “about 10-30”) refers to all values ​​in the series or the endpoints of the range, respectively.

[0018] As used herein, the terms “administer,” “administering,” or “administration” mean the direct administration of a compound or a pharmaceutically acceptable salt or ester of said compound to a patient, or a composition comprising said compound or a pharmaceutically acceptable salt or ester of said compound.

[0019] The terms “effective amount” and “therapeutic effective amount” are used interchangeably in this disclosure and refer to the amount of a compound or its salts, solvates, or esters that, when administered to a patient, would produce the desired effect. For example, an effective amount of a triptan is the amount required to alleviate at least one symptom of a patient’s ASD, such as the amount required to improve ASD-related irritability, reduce ASD-related aggression, or improve a patient’s social abilities. The actual amount including “effective amount” or “therapeutic effective amount” will vary depending on a variety of conditions, including but not limited to the triptan administered, the severity of the disorder, the patient’s body size and health status, and the route of administration. A skilled physician can readily determine the appropriate amount using the methods described herein and as known in the medical field.

[0020] As used herein, the phrase “pharmaceutically acceptable” refers to compounds, materials, compositions, and / or dosage forms that are suitable for use in human and animal tissue contact with reasonable medical judgment without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0021] As used herein, the term "salt" includes pharmaceutically acceptable salts, such as alkali metal salts commonly used to form free acids and addition salts used to form free bases. The properties of the salt are not critical, provided it is pharmaceutically acceptable. The term "salt" also includes solvates of addition salts (such as hydrates) and polymorphs of addition salts. Suitable pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Examples of such inorganic acids are hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid, and phosphoric acid. Suitable organic acids can be selected from fatty acids, alicyclic acids, aromatic acids, aryl fatty acids, and carboxylic acids and sulfonic acids containing heterocyclic groups, such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, methanesulfonic acid, stearic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, mandelic acid, embonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, pantothenic acid, toluenesulfonic acid, 2-hydroxyethanesulfonic acid, sulfanilic acid, cyclohexylaminosulfonic acid, alginic acid, 3-hydroxybutyric acid, galactosidic acid, and galacturonic acid.

[0022] As used herein with respect to patients, the term "treatment" refers to the improvement of at least one symptom of a patient's disorder. Treatment can be an improvement or at least a partial improvement of the disorder. For example, treating a patient's ASD is done when the methods described reduce at least one symptom of the patient's autism spectrum disorder (e.g., irritability, aggression, or reduced social skills).

[0023] As used herein, the term "therapeutic effect" refers to the desired or beneficial effect provided by the method and / or the composition. For example, a method for treating autism spectrum disorder provides a therapeutic effect when the method improves at least one symptom of a patient's ASD, such as improving ASD-related irritability, improving ASD-related aggression, or improving social skills. Detailed Implementation

[0024] Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, restricted interests, and repetitive behaviors. Individuals on the autism spectrum experience a wide range of degrees and types of impairment, from mild to severe. While early detection and intervention are encouraged to maximize benefits and reduce the severity of symptoms, individuals of any age can benefit from interventions and therapies that can alleviate symptoms and improve skills and abilities. Appropriate subjects for the methods described herein include, but are not limited to, individuals diagnosed with or suspected of having autism spectrum disorder.

[0025] In one respect, this disclosure provides a method for treating one or more symptoms of ASD by administering a therapeutically effective amount of a triptan to a patient in need.

[0026] In some embodiments, this disclosure provides a method for treating symptoms of a condition selected from Asperger's syndrome or pervasive developmental disorder unclassified (PDD-NOS) by administering a therapeutically effective amount of a triptan to a patient in need.

[0027] In some embodiments, this disclosure provides methods for improving one or more symptoms associated with ASD by administering a therapeutically effective amount of triptan to a patient in need. In some embodiments, the methods of this disclosure provide improvements in social competence compared to pre-treatment levels. In some embodiments, the methods of this disclosure provide a reduction in ASD-related irritability compared to pre-treatment levels. In some embodiments, the methods of this disclosure provide a reduction in ASD-related aggression compared to pre-treatment levels.

[0028] Triptans

[0029] Triptane drugs used in the method of the present invention can be formed as part of a pharmaceutical composition by combining a triptan drug or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier. Additionally, the composition may include additives selected from adjuvants, excipients, diluents, release modifiers, and stabilizers. The composition may be an immediate-release formulation, a delayed-release formulation, a sustained-release formulation, or a prolonged-release formulation.

[0030] Triptans belong to the serotonin receptor subtype-selective drug class. Triptans target the 5-HT receptor agonist, which belongs to the serotonin (5-HT) system.1B 5-HT 1D and 5-HT 1F The receptors exhibit selective activity. Triptans demonstrate vasoconstrictive properties, which are mediated by their effect on 5-HT in arterial smooth muscle. 1B The action is mediated by triptans. Vasoconstriction induced by triptans leads to a dose-dependent increase in blood flow velocity in cerebral vessels. Triptans are believed to inhibit aberrant activation of peripheral nociceptors. It is speculated that triptans reduce plasma protein extravasation (PPE) by inhibiting nociceptor activation and preventing the peripheral release of vasoactive peptides, including substance P and calcitonin gene-related peptide (CGRP). Triptans also have binding sites in the central nervous system. Therefore, triptans may exhibit effects on the central nervous system. At the time of this publication, triptans have been approved by the FDA for the treatment of migraines.

[0031] Since the discovery of abnormal blood 5-HT levels as the first biomarker of autism more than 50 years ago, the serotonin system has been involved in the pathophysiology of autism (Schain et al. J Pediatr. March 1961; 58:315-20). The main source of 5-HT in the brain is the dorsal raphe nucleus (DRN) of the midbrain, which projects extensively to the cortex, amygdala, and hypothalamus, and to other subcortical structures related to emotional processing and social behavior. Dense serotonin from the DRN can project and innervate the nucleus accumbens (NAc) (a well-preserved basal forebrain structure), which acts as an integrator of motivational signals before selecting behavioral actions (Kravitz et al. Physiology (Bethesda. June 2012; 27(3):167-77.). In the context of social interaction, it is believed that NAc reward processing controls the choice of social behavior and social avoidance behavior (Pfaff. Trends Neurosci. 2019 July; 42(7):448-457.). Evidence from preclinical studies supports the key role of 5-HT signaling in social behavior and social reward (Kane et al. PLoS One. 2012; 7(11):e48975.; Challis et al. J Neurosci. 2013 Aug 28; 33(35):13978-88,13988a.; Li et al. Nat Commun. 2016 Jan 28; 7:10503.). Furthermore, abnormal processing of reward was observed in NAc in fMRI imaging studies of children with ASD (Clements et al. JAMA Psychiatry. 2018 Aug 1; 75(8):797-808. doi:10.1001 / jamapsychiatry.2018.1100.).

[0032] In the human brain, 5-HT1B is highly expressed in NAc (Garcia-Alloza et al. Neuropsychologia. 2005; 43(3):442-9.; Varnas et al. Hum Brain Mapp. 2004 Jul; 22(3):246-60.; Varnas et al. Synapse. 56:21-8.). It is an inhibitory G protein-coupled receptor located at the axon terminal, which plays a role in inhibiting the release of neurotransmitters (Sari. Neurosci Biobehav Rev. 2004 Oct; 28(6):565-82.). As an autoreceptor, 5-HT1B inhibits the release of 5-HT, but it also plays an important role as an heteroreceptor to inhibit the release of other neurotransmitters, including glutamate, GABA, dopamine, and acetylcholine (Boscher et al. (1994) Neuroscience 58:167–182.). According to this publication, the 5-HT1B agonist effect of the triptans described herein modulates the behavioral symptoms of ASD.

[0033] In some embodiments, the triptans used in the formulations and methods of this disclosure are selected from sumatriptan, zolmitriptan, naratriptan, rizatriptan, amotriptan, furotriptan, eletriptan, donitriptan, avetriptan, or pharmaceutically acceptable salts thereof.

[0034] In some embodiments, the triptan used in the formulations and methods of this disclosure is sumatriptan or a pharmaceutically acceptable salt thereof. In some embodiments, the triptan used in the formulations and methods of this disclosure is sumatriptan hydrochloride. In some embodiments, the triptan used in the formulations and methods of this disclosure is sumatriptan succinate.

[0035] In some implementations, the method described in this disclosure includes administering a therapeutically effective amount of zolmitriptan or a pharmaceutically acceptable salt thereof to a patient in need.

[0036] In some embodiments, the method described in this disclosure includes administering a therapeutically effective amount of naratriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the pharmaceutically acceptable salt is naratriptan hydrochloride.

[0037] In some embodiments, the method described in this disclosure includes administering a therapeutically effective amount of rizatriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the pharmaceutically acceptable salt is rizatriptan benzoate.

[0038] In some implementations, the method described in this disclosure includes administering a therapeutically effective amount of amotriptan or a pharmaceutically acceptable salt thereof to a patient in need.

[0039] In some implementations, the method described in this disclosure includes administering a therapeutically effective amount of furostrecan or a pharmaceutically acceptable salt thereof to a patient in need.

[0040] In some embodiments, the method described in this disclosure includes administering a therapeutically effective amount of eletriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the pharmaceutically acceptable salt is eletriptan hydrobromide.

[0041] Preparations

[0042] The methods disclosed herein can employ various pharmaceutical compositions to be administered to a patient (e.g., a human or an animal) in a unit dosage form (such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, inhalable dry powders, dispersants, solutions or suspensions, and oral solutions or suspensions, and oil-in-water emulsions) containing an appropriate amount of a triptan or a pharmaceutically acceptable salt thereof.

[0043] In some embodiments, the pharmaceutical compositions of this disclosure are prepared for oral administration. In some embodiments, the pharmaceutical compositions are formulated by combining one or more triptan drugs and a pharmaceutically acceptable carrier. Some of these carriers enable the formulation of the pharmaceutical compositions into tablets, pills, sugar-coated pills, capsules, liquids, gels, syrups, slurries, suspensions, etc., for oral ingestion by a subject. Suitable excipients include, but are not limited to, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, astragalus gum, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). In some embodiments, such mixtures are optionally milled and excipients are optionally added. In some embodiments, the pharmaceutical composition is formed to obtain a tablet or sugar-coated pill core. In some embodiments, a disintegrant (e.g., croscarmellose, agar, or alginate or a salt thereof, such as sodium alginate) is added.

[0044] Suitable aqueous carriers for use in this disclosure include, but are not limited to, water, ethanol, alcoholic / aqueous solutions, glycerol, emulsions, or suspensions, including saline and buffer media. Oral carriers may be elixirs, syrups, capsules, tablets, etc.

[0045] The liquid carriers suitable for use in this disclosure can be used to prepare solutions, suspensions, emulsions, syrups, and elixirs. Triptane drugs can be dissolved or suspended in pharmaceutically acceptable liquid carriers, such as water, organic solvents, mixtures of both, or pharmaceutically acceptable oils or fats. The liquid carriers may contain other suitable pharmaceutical additives, such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavorings, suspending agents, thickeners, colorants, viscosity modifiers, stabilizers, or osmotic pressure modifiers.

[0046] Suitable liquid carriers for use in this application include, but are not limited to, water (partially containing the above-mentioned additives, such as cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, such as diols) and their derivatives, and oils (such as fractionated coconut oil and peanut oil).

[0047] In some embodiments, the pharmaceutical compositions of this disclosure are prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, etc.). In some of these embodiments, the pharmaceutical composition comprises a carrier and is formulated in an aqueous solution (e.g., water) or a physiologically compatible buffer (e.g., Hanks' solution, Ringer's solution, or saline buffer). In some embodiments, other components are included (e.g., components that aid in dissolution or act as preservatives). In some embodiments, an injectable suspension is prepared using a suitable liquid carrier, suspending agent, etc. Some injectable pharmaceutical compositions are presented in unit dosage forms, such as in ampoules or in multi-dose containers. Some injectable pharmaceutical compositions are suspensions, solutions, or emulsions in oily or aqueous media and may contain formulations such as suspending agents, stabilizers, and / or dispersants. Certain solvents suitable for use in injectable pharmaceutical compositions include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil; synthetic fatty acid esters, such as ethyl oleate or triglycerides; and liposomes. Aqueous injectable suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, such suspensions may also contain suitable stabilizers or reagents that increase the solubility of the drug to allow for the preparation of high-concentration solutions.

[0048] Sterile injectable formulations can also be sterile injectable solutions or suspensions (such as solutions in 1,3-butanediol) in non-toxic, parenteral diluents or solvents, or prepared as lyophilized powders. Acceptable media and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. Additionally, sterile non-volatile oils can routinely be used as solvents or suspending media. For this purpose, any mild non-volatile oil can be used, including synthetic monoglycerides or diglycerides. Furthermore, fatty acids (such as oleic acid) can also be used to prepare injectable formulations. Formulations for intravenous administration may contain solutions in sterile isotonic aqueous buffer solutions. If necessary, formulations may also include solubilizers and local anesthetics to relieve pain at the injection site. Typically, the components are provided separately or mixed together in unit dosage forms, such as as dried lyophilized powders or anhydrous concentrates in hermetically sealed containers, such as ampoules or capsules indicating the amount of active agent. When the compound is to be administered by infusion, it can be prepared using an infusion bottle containing sterile pharmaceutical-grade water, saline, or dextrose / water. When the compound is to be administered by injection, a single ampoule of sterile water for injection or saline can be provided so that the components can be mixed before administration.

[0049] Suitable formulations further include aqueous sterile injectable solutions and non-aqueous sterile injectable solutions, the sterile injectable solutions potentially containing antioxidants, buffers, bacteriostatic agents, bactericidal antibiotics, and solutes that make the formulation isotonic with the body fluids of the intended recipient; as well as aqueous sterile suspensions and non-aqueous sterile suspensions, the sterile suspensions potentially including suspending agents and thickeners.

[0050] In some embodiments, the pharmaceutical compositions of this disclosure are formulated as depot formulations. Some of these depot formulations generally have a longer duration of action than non-depot formulations. In some embodiments, such formulations are administered by implantation (e.g., subcutaneous or intramuscular) or by intramuscular injection. In some embodiments, the depot formulation is prepared using suitable polymeric or hydrophobic materials (e.g., emulsions in acceptable oils) or ion exchange resins, or is prepared as a slightly soluble derivative (e.g., prepared as a slightly soluble salt).

[0051] In some embodiments, the pharmaceutical compositions of this disclosure are prepared for intranasal administration.

[0052] Application and administration

[0053] This disclosure provides methods for treating symptoms associated with autism spectrum disorder (ASD) by administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, an effective amount is an amount sufficient to eliminate or significantly reduce one or more symptoms associated with ASD, or to alleviate those symptoms (e.g., reduce symptoms such as irritability, aggression, or improve social skills compared to pre-treatment symptoms). In some embodiments, an effective amount is an amount sufficient to eliminate or significantly reduce ASD-related irritability compared to pre-treatment levels. In some embodiments, an effective amount is an amount sufficient to eliminate or significantly improve social skills compared to pre-treatment levels.

[0054] The reduction of autism symptoms in patients with ASD can be determined using a variety of methods. In some implementation schemes, the effectiveness of a dosage regimen can be determined by evaluation based on the OSU Autism Rating Scale (OARS-5), the Vinland Adaptive Behavior Scale, ADOS-2, the CGI-S and CGI-C Social Deficit Subscales, the Autism Behavior Questionnaire, and the Childhood Autism Rating Scale, the Social Response Scale, the Abnormal Behavior Checklist, the Social Developmental Disorders Behavior Checklist, the Top 3 Caregiver Attention, the Autism Behavior Questionnaire, and the Autism Treatment Evaluation Checklist (ATEC), the Social Response Scale version 2 (SRS-2), or any combination thereof.

[0055] According to some embodiments of this disclosure, the frequency and dosage of each administration of a triptan are selected to provide therapeutic effects for one or more of the symptoms associated with ASD.

[0056] In some implementations, the frequency and dosage of triptans are selected to provide therapeutic effects for irritability symptoms associated with ASD.

[0057] In some implementations, the frequency and dosage of triptans are selected to provide therapeutic effects for attack symptoms associated with ASD.

[0058] In some implementations, the frequency and dosage of triptans are selected to provide therapeutic effects for social competence symptoms associated with ASD.

[0059] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering a therapeutically effective amount of sumatriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need amounts of sumatriptan or a pharmaceutically acceptable salt thereof in the following quantities: about 1 mg to about 200 mg, including about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 15 mg, about 20 mg, about 22 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, etc. mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, and about 100 mg, about 105 mg, about 110.0 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, and about 200 mg, including all values ​​and ranges therein. In some embodiments, about 25 mg to about 200 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some implementations, about 25 mg to about 100 mg of sumatriptan or a pharmaceutically acceptable salt is administered to patients in need.

[0060] In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of sumatriptan or a pharmaceutically acceptable salt thereof: about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 15 mg, about 20 mg, about 22 mg, about 25 mg, about 30 mg, about 35 mg, about 4 mg, or about 4 mg. 0mg, about 45mg, about 50mg, about 55mg, about 60mg, about 65mg, about 70mg, about 75mg, about 80mg, about 85mg, about 90mg, about 95mg, about 100mg, about 105mg, about 110.0mg, about 115mg, about 120mg, about 125mg, about 130mg, about 135mg, about 140mg, about 145mg, about 150mg, about 155mg, about 160mg, about 165mg, about 170mg, about 175mg, about 180mg, about 185mg, about 190mg, about 195mg, or about 200mg.

[0061] In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 6 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 5 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0062] In some implementations, approximately 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some implementations, approximately 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0063] In some embodiments, sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0064] In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 3 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0065] In some embodiments, about 6 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 6 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily.

[0066] In some embodiments, about 5 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 5 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily.

[0067] In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 10 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0068] In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 20 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0069] In some embodiments, about 22 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 22 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 22 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0070] In some embodiments, about 25 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 25 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 25 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0071] In some embodiments, about 50 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 50 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 50 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0072] In some embodiments, about 100 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 100 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 100 mg of sumatriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0073] In some embodiments, the methods of this disclosure provide plasma levels of sumatriptan (e.g., mean steady-state plasma levels) that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of sumatriptan provided by the methods of this disclosure range from about 10 ng / mL to about 300 ng / mL, including about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, about 130 ng / mL, and about... 140 ng / ml, approximately 150 ng / ml, approximately 160 ng / ml, approximately 170 ng / ml, approximately 180 ng / ml, approximately 190 ng / ml, approximately 200 ng / ml, approximately 210 ng / ml, approximately 220 ng / ml, approximately 230 ng / ml, approximately 240 ng / ml, approximately 250 ng / ml, approximately 260 ng / ml, approximately 270 ng / ml, approximately 280 ng / ml, approximately 290 ng / ml, and approximately 300 ng / ml, including all values ​​and ranges therein.

[0074] In some embodiments, the method of this disclosure provides the following plasma Cmax for sumatriptan: from about 10 ng / mL to about 150 ng / mL, including about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, about 130 ng / mL, about 140 ng / mL, and about 150 ng / mL, including all values ​​and ranges therebetween. In some embodiments, the method of this disclosure provides plasma Cmax for sumatriptan from about 10 ng / mL to about 100 ng / mL.

[0075] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering a therapeutically effective amount of zolmitriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need amounts of zolmitriptan or a pharmaceutically acceptable salt thereof in the following quantities: about 1.0 mg to about 50 mg, including about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, etc. Approximately 10.0 mg, approximately 10.5 mg, approximately 11.0 mg, approximately 11.5 mg, approximately 12.0 mg, approximately 12.5 mg, approximately 13.0 mg, approximately 13.5 mg, approximately 14.0 mg, approximately 14.5 mg, approximately 15.0 mg, approximately 15.5 mg, approximately 16.0 mg, approximately 16.5 mg, approximately 17.0 mg, approximately 17.5 mg, approximately 18.0 mg, approximately 18.5 mg, approximately 19.0 mg, approximately 19.5 mg, approximately 20.0 mg, approximately 20.5 mg, approximately 21.0 mg, approximately 21.5 mg, approximately 22.0 mg, approximately 22.5 mg Approximately 23.0 mg, approximately 23.5 mg, approximately 24.0 mg, approximately 24.5 mg, approximately 25.0 mg, approximately 25.5 mg, approximately 26.0 mg, approximately 26.5 mg, approximately 27.0 mg, approximately 27.5 mg, approximately 28.0 mg, approximately 28.5 mg, approximately 29.0 mg, approximately 29.5 mg, approximately 30.0 mg, approximately 30.5 mg, approximately 31 mg, approximately 31.5 mg, approximately 32 mg, approximately 32.5 mg, approximately 33 mg, approximately 33.5 mg, approximately 34 mg, approximately 34.5 mg, approximately 35 mg, approximately 35.5 mg, approximately 36 mg, approximately 36. 5 mg, about 37 mg, about 37.5 mg, about 38 mg, about 38.5 mg, about 39 mg, about 39.5 mg, about 40 mg, about 40.5 mg, about 41 mg, about 41.5 mg, about 42 mg, about 42.5 mg, about 43 mg, about 43.5 mg, about 44 mg, about 44.5 mg, about 45.0 mg, about 45.5 mg, about 46 mg, about 46.5 mg, about 47 mg, about 47.5 mg, about 48 mg, about 48.5 mg, about 49.0 mg, about 49.5 mg, and about 50 mg, including all values ​​and ranges therein. In some embodiments, about 1.25 mg to about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 1.7 mg to about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of zolmitriptan or a pharmaceutically acceptable salt thereof: about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg. mg, approximately 10.5 mg, approximately 11.0 mg, approximately 11.5 mg, approximately 12.0 mg, approximately 12.5 mg, approximately 13.0 mg, approximately 13.5 mg, approximately 14.0 mg, approximately 14.5 mg, approximately 15.0 mg, approximately 15.5 mg, approximately 16.0 mg, approximately 16.5 mg, approximately 17.0 mg, approximately 17.5 mg, approximately 18.0 mg, approximately 18.5 mg, approximately 19.0 mg, approximately 19.5 mg, approximately 20.0 mg, approximately 20.5 mg, approximately 21.0 mg, approximately 21.5 mg, approximately 22.0 mg, approximately 22.5 mg Approximately 23.0 mg, approximately 23.5 mg, approximately 24.0 mg, approximately 24.5 mg, approximately 25.0 mg, approximately 25.5 mg, approximately 26.0 mg, approximately 26.5 mg, approximately 27.0 mg, approximately 27.5 mg, approximately 28.0 mg, approximately 28.5 mg, approximately 29.0 mg, approximately 29.5 mg, approximately 30.0 mg, approximately 30.5 mg, approximately 31 mg, approximately 31.5 mg, approximately 32 mg, approximately 32.5 mg, approximately 33 mg, approximately 33.5 mg, approximately 34 mg, approximately 34.5 mg, approximately 35 mg, approximately 35.5 mg, approximately 36 mg mg, approximately 36.5 mg, approximately 37 mg, approximately 37.5 mg, approximately 38 mg, approximately 38.5 mg, approximately 39 mg, approximately 39.5 mg, approximately 40 mg, approximately 40.5 mg, approximately 41 mg, approximately 41.5 mg, approximately 42 mg, approximately 42.5 mg, approximately 43 mg, approximately 43.5 mg, approximately 44 mg, approximately 44.5 mg, approximately 45.0 mg, approximately 45.5 mg, approximately 46 mg, approximately 46.5 mg, approximately 47 mg, approximately 47.5 mg, approximately 48 mg, approximately 48.5 mg, approximately 49.0 mg, approximately 49.5 mg, or approximately 50 mg.

[0076] In some implementations, the following amounts of zolmitriptan or pharmaceutically acceptable salt are administered to the patient three times daily: about 2.0 mg to about 15 mg, including about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, and about 15 mg, including all values ​​and ranges therein. In some implementations, patients are given about 2.0 mg to about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times a day.

[0077] In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0078] In some implementations, zolmitriptan or a pharmaceutically acceptable salt thereof is administered to patients in need once daily. In some implementations, zolmitriptan or a pharmaceutically acceptable salt thereof is administered to patients in need twice daily. In some implementations, zolmitriptan or a pharmaceutically acceptable salt thereof is administered to patients in need three times daily.

[0079] In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 1.25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0080] In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0081] In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0082] In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0083] In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0084] In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 15 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0085] In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 20 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0086] In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 25 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0087] In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 30 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0088] In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 35 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0089] In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 40 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0090] In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 45 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0091] In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof is administered three times daily.

[0092] In some embodiments, the method of treating autism-related symptoms according to this disclosure further includes a step of gradually adjusting the dose of zolmitriptan or a pharmaceutically acceptable salt thereof for at least about one week until steady state is reached in the patient. In some embodiments, the gradual adjustment is performed for about two weeks until steady state is reached in the patient. In some embodiments, the gradual adjustment is performed for about seven days to about 30 days until steady state is reached in the patient. In some embodiments, the gradual adjustment is performed for about 12 days to about 20 days until steady state is reached in the patient.

[0093] In some embodiments, escalating doses of zolmitriptan or a pharmaceutically acceptable salt thereof are administered during step-up until a steady state is reached in the patient. In some embodiments, escalating doses of zolmitriptan or a pharmaceutically acceptable salt thereof are administered during step-up until an effective dose of about 5 mg, about 7.5 mg, about 10.0 mg, about 12.5 mg, or about 15 mg is achieved in the patient.

[0094] In some implementations, the gradual adjustment begins with a dose of approximately 2.5 mg administered three times daily. In other implementations, the gradual adjustment begins with a dose of approximately 5 mg administered three times daily.

[0095] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes starting with an administration of about 2.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily, and gradually adjusting to an administration of about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily. In some embodiments, the method of treating autism-related symptoms according to this disclosure includes starting with an administration of about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily, and gradually adjusting to an administration of about 7.5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily. In some embodiments, the method of treating autism-related symptoms according to this disclosure includes starting with an administration of about 5 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily, and gradually adjusting to an administration of about 10 mg of zolmitriptan or a pharmaceutically acceptable salt thereof three times daily.

[0096] In some embodiments, the methods of this disclosure provide CSF levels of zolmitriptan that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective CSF levels of zolmitriptan provided by the methods of this disclosure range from about 0.05 ng / mL to about 2 ng / mL, including about 0.05 ng / mL, about 0.075 ng / mL, about 0.1 ng / mL, about 0.125 ng / mL, about 0.15 ng / mL, about 0.175 ng / mL, about 0.2 ng / mL, about 0.25 ng / mL, about 0.3 ng / mL, about 0.35 ng / mL, about 0.4 ng / mL, about 0.45 ng / mL, about 0.5 ng / mL, about 0.55 ng / mL, about 0.6 ng / mL, about 0.65 ng / mL, about 0.7 ng / mL, about 0.75 ng / mL, and about 0. Approximately 0.85 ng / mL, approximately 0.9 ng / mL, approximately 0.95 ng / mL, approximately 1 ng / mL, approximately 1.1 ng / mL, approximately 1.15 ng / mL, approximately 1.2 ng / mL, approximately 1.25 ng / mL, approximately 1.3 ng / mL, approximately 1.35 ng / mL, approximately 1.4 ng / mL, approximately 1.45 ng / mL, approximately 1.5 ng / mL, approximately 1.55 ng / mL, approximately 1.6 ng / mL, approximately 1.65 ng / mL, approximately 1.7 ng / mL, approximately 1.75 ng / mL, approximately 1.8 ng / mL, approximately 1.85 ng / mL, approximately 1.9 ng / mL, approximately 1.95 ng / mL, and approximately 2 ng / mL, including all values ​​and ranges therebetween. In some embodiments, the therapeutically effective CSF levels of zolmitriptan provided by the methods of this disclosure range from approximately 0.078 ng / mL to approximately 1.24 ng / mL. In some implementations, the therapeutically effective CSF levels of zolmitriptan provided by the methods of this disclosure range from about 0.103 ng / mL to about 0.93 ng / mL.

[0097] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering naratriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need amounts of naratriptan or a pharmaceutically acceptable salt thereof in the following quantities: about 0.5 mg to about 20 mg, including about 0.5 mg, about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, and about... 9.5 mg, about 10.0 mg, about 10.5 mg, about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, and about 20.0 mg, including all values ​​and ranges therein. In some embodiments, about 0.5 mg to about 9 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 1 mg to about 5 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of natratriptan or a pharmaceutically acceptable salt thereof: about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg. The dosages are approximately 10.0 mg, 10.5 mg, 11.0 mg, 11.5 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16.0 mg, 16.5 mg, 17.0 mg, 17.5 mg, 18.0 mg, 18.5 mg, 19.0 mg, 19.5 mg, or 20.0 mg. In some embodiments, approximately 1 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, approximately 2.5 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0098] In some implementations, naratriptan or a pharmaceutically acceptable salt thereof is administered to patients in need once daily. In some implementations, naratriptan or a pharmaceutically acceptable salt thereof is administered to patients in need twice daily. In some implementations, naratriptan or a pharmaceutically acceptable salt thereof is administered to patients in need three times daily.

[0099] In some embodiments, about 1 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 1 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 1 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 1 mg of natratriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0100] In some embodiments, about 2.5 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 2.5 mg of naratriptan or a pharmaceutically acceptable salt thereof is administered twice daily.

[0101] In some embodiments, the methods of this disclosure provide plasma levels of naratriptan (e.g., mean steady-state plasma levels) that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of naratriptan provided by the methods of this disclosure range from about 5 ng / mL to about 300 ng / mL, including about 5 ng / mL, about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, about 130 ng / mL, etc. The ranges are approximately 140 ng / ml, 150 ng / ml, 160 ng / ml, 170 ng / ml, 180 ng / ml, 190 ng / ml, 200 ng / ml, 210 ng / ml, 220 ng / ml, 230 ng / ml, 240 ng / ml, 250 ng / ml, 260 ng / ml, 270 ng / ml, 280 ng / ml, 290 ng / ml, and 300 ng / ml, including all values ​​and ranges therein. In some embodiments, the therapeutically effective plasma levels of naratriptan provided by the methods of this disclosure range from approximately 10 ng / mL to approximately 300 ng / ml.

[0102] In some embodiments, the method of this disclosure provides naratriptan with the following plasma Cmax: from about 5 ng / mL to about 300 ng / mL, including about 5 ng / mL, 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, about 130 ng / mL. Approximately 140 ng / ml, approximately 150 ng / ml, approximately 160 ng / ml, approximately 170 ng / ml, approximately 180 ng / ml, approximately 190 ng / ml, approximately 200 ng / ml, approximately 210 ng / ml, approximately 220 ng / ml, approximately 230 ng / ml, approximately 240 ng / ml, approximately 250 ng / ml, approximately 260 ng / ml, approximately 270 ng / ml, approximately 280 ng / ml, approximately 290 ng / ml, and approximately 300 ng / ml, including all values ​​and ranges therebetween. In some embodiments, the method of this disclosure provides a plasma Cmax of approximately 12 ng / mL nalaratriptan.

[0103] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering a therapeutically effective amount of rizatriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need amounts of rizatriptan or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 200 mg, including about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, and about 7.0 mg. Approximately 7.5mg, approximately 8.0mg, approximately 8.5mg, approximately 9.0mg, approximately 9.5mg, approximately 10.0mg, approximately 10.5mg, approximately 11.0mg, approximately 11.5mg, approximately 12.0mg, approximately 12.5mg, approximately 13.0mg, approximately 13.5mg, approximately 14.0mg, approximately 14.5mg, approximately 15.0mg, approximately 15.5mg, approximately 16.0mg, approximately 16.5mg, approximately 17 0mg, approximately 17.5mg, approximately 18.0mg, approximately 18.5mg, approximately 19.0mg, approximately 19.5mg, approximately 20.0mg, approximately 25mg, approximately 30mg, approximately 35mg, approximately 40mg, approximately 45mg, approximately 50mg, approximately 55mg, approximately 60mg, approximately 65mg, approximately 70mg, approximately 75mg, approximately 80mg, approximately 85mg, approximately 90mg, approximately 95mg, approximately 100mg, approximately 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, and about 200 mg, including all values ​​and ranges therein. In some embodiments, about 11 mg to about 200 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 5 mg to about 30 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 5 mg to about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of rizatriptan or a pharmaceutically acceptable salt thereof: about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17. 0mg, approximately 17.5mg, approximately 18.0mg, approximately 18.5mg, approximately 19.0mg, approximately 19.5mg, approximately 20.0mg, approximately 25mg, approximately 30mg, approximately 35mg, approximately 40mg, approximately 45mg, approximately 50mg, approximately 55mg, approximately 60mg, approximately 65mg, approximately 70mg, approximately 75mg, approximately 80mg, approximately 85mg, approximately 90mg, approximately 95mg, approximately 1 Approximately 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 195 mg, or 200 mg. In some embodiments, approximately 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, approximately 10.0 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0104] In some implementations, rizatriptan or a pharmaceutically acceptable salt thereof is administered to patients in need once daily. In some implementations, rizatriptan or a pharmaceutically acceptable salt thereof is administered to patients in need twice daily. In some implementations, rizatriptan or a pharmaceutically acceptable salt thereof is administered to patients in need three times daily.

[0105] In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 5 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0106] In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 10 mg of rizatriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0107] In some embodiments, the methods of this disclosure provide plasma levels of rizatriptan (e.g., mean steady-state plasma levels) that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of rizatriptan provided by the methods of this disclosure range from about 5 ng / mL to about 300 ng / mL, including about 5 ng / mL, about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, and about 130 ng / mL. The values ​​are approximately 140 ng / ml, 150 ng / ml, 160 ng / ml, 170 ng / ml, 180 ng / ml, 190 ng / ml, 200 ng / ml, 210 ng / ml, 220 ng / ml, 230 ng / ml, 240 ng / ml, 250 ng / ml, 260 ng / ml, 270 ng / ml, 280 ng / ml, 290 ng / ml, and 300 ng / ml, including all values ​​and ranges in between.

[0108] In some embodiments, the method of this disclosure provides rizatriptan with the following plasma Cmax: from about 5 ng / mL to about 300 ng / mL, including about 5 ng / mL, 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, about 130 ng / mL. Approximately 140 ng / ml, approximately 150 ng / ml, approximately 160 ng / ml, approximately 170 ng / ml, approximately 180 ng / ml, approximately 190 ng / ml, approximately 200 ng / ml, approximately 210 ng / ml, approximately 220 ng / ml, approximately 230 ng / ml, approximately 240 ng / ml, approximately 250 ng / ml, approximately 260 ng / ml, approximately 270 ng / ml, approximately 280 ng / ml, approximately 290 ng / ml, and approximately 300 ng / ml, including all values ​​and ranges therebetween. In some embodiments, the method of this disclosure provides a Cmax of approximately 5 ng / mL to approximately 50 ng / ml of rizatriptan. In some embodiments, the method of this disclosure provides a Cmax of approximately 6 ng / mL, approximately 13 ng / mL, approximately 29 ng / mL, or approximately 44.8 ng / mL of rizatriptan.

[0109] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering a therapeutically effective amount of amotriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need amounts of amotriptan or a pharmaceutically acceptable salt thereof in the following quantities: about 5.0 mg to about 30.0 mg, including about 5.0 mg, about 5.25 mg, about 5.5 mg, about 5.75 mg, about 6.0 mg, about 6.25 mg, about 6.5 mg, about 6.75 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, and about 15 mg, about 15.5 mg, about... 15.75 mg, about 16.0 mg, about 16.25 mg, about 16.5 mg, about 16.75 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 20.5 mg, about 21 mg, about 21.5 mg, about 22 mg, about 22.5 mg, about 23 mg, about 23.5 mg, about 24 mg, about 24.5 mg, about 25 mg, about 25.5 mg, about 26 mg, about 26.5 mg, about 27 mg, about 27.5 mg, about 28 mg, about 28.5 mg, about 29 mg, about 29.5 mg, and about 30 mg, including all values ​​and ranges therein. In some embodiments, about 6 mg to about 25 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered to the patient in need.In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of amotriptan or a pharmaceutically acceptable salt thereof: about 5.0 mg, about 5.25 mg, about 5.5 mg, about 5.75 mg, about 6.0 mg, about 6.25 mg, about 6.5 mg, about 6.75 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11 mg, about 11.5 mg, about 12 mg, about 12.5 mg, about 13 mg, about 13.5 mg, about 14 mg, about 14.5 mg, about 15 mg, about 15.5 mg, about 1 5.75 mg, about 16.0 mg, about 16.25 mg, about 16.5 mg, about 16.75 mg, about 17.0 mg, about 17.5 mg, about 18.0 mg, about 18.5 mg, about 19.0 mg, about 19.5 mg, about 20.0 mg, about 20.5 mg, about 21 mg, about 21.5 mg, about 22 mg, about 22.5 mg, about 23 mg, about 23.5 mg, about 24 mg, about 24.5 mg, about 25 mg, about 25.5 mg, about 26 mg, about 26.5 mg, about 27 mg, about 27.5 mg, about 28 mg, about 28.5 mg, about 29 mg, about 29.5 mg, and about 30 mg. In some embodiments, about 6.25 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some implementations, approximately 12.5 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need.

[0110] In some implementations, amotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need once daily. In some implementations, amotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need twice daily. In some implementations, amotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need three times daily.

[0111] In some embodiments, about 6.25 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 6.25 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 6.25 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 6.25 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0112] In some embodiments, about 12.5 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 12.5 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 12.5 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 12.5 mg of amotriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0113] In some embodiments, the methods of this disclosure provide plasma levels of amotriptan (e.g., mean steady-state plasma levels) that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of amotriptan provided by the methods of this disclosure range from about 20 ng / ml to about 600 ng / ml, including about 20 ng / ml, about 30 ng / ml, about 40 ng / ml, about 50 ng / ml, about 60 ng / ml, about 70 ng / ml, about 80 ng / ml, about 90 ng / ml, about 100 ng / ml, about 110 ng / ml, about 120 ng / ml, and about 1... 30 ng / ml, approximately 140 ng / ml, approximately 150 ng / ml, approximately 160 ng / ml, approximately 170 ng / ml, approximately 180 ng / ml, approximately 190 ng / ml, approximately 200 ng / ml, approximately 210 ng / ml, approximately 220 ng / ml, approximately 230 ng / ml, approximately 240 ng / ml, approximately 250 ng / ml, approximately 260 ng / ml, approximately 270 ng / ml, approximately 280 ng / ml, approximately 290 ng / ml g / ml, approximately 300 ng / ml, approximately 310 ng / ml, approximately 320 ng / ml, approximately 330 ng / ml, approximately 340 ng / ml, approximately 350 ng / ml, approximately 360 ng / ml, approximately 370 ng / ml, approximately 380 ng / ml, approximately 390 ng / ml, approximately 400 ng / ml, approximately 410 ng / ml, approximately 420 ng / ml, approximately 430 ng / ml, approximately 440 ng / ml, approximately 450 ng / ml l, approximately 460 ng / ml, approximately 470 ng / ml, approximately 480 ng / ml, approximately 490 ng / ml, approximately 500 ng / ml, approximately 510 ng / ml, approximately 520 ng / ml, approximately 530 ng / ml, approximately 540 ng / ml, approximately 550 ng / ml, approximately 560 ng / ml, approximately 570 ng / ml, approximately 580 ng / ml, approximately 590 ng / ml, and approximately 600 ng / mL, including all values ​​and ranges therein.

[0114] In some embodiments, the method of this disclosure provides amotriptan with the following plasma Cmax: from about 20 ng / mL to about 600 ng / mL, including about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 110 ng / mL, about 120 ng / mL, and about 130 ng / mL. / ml, approximately 140ng / ml, approximately 150ng / ml, approximately 160ng / ml, approximately 170ng / ml, approximately 180ng / ml, approximately 190ng / ml, approximately 200ng / ml, approximately 210ng / ml, approximately 220ng / ml, approximately 230ng / ml, approximately 240ng / ml, approximately 250ng / ml, approximately 260ng / ml, approximately 270ng / ml, approximately 280ng / ml, approximately 290ng / ml 1. Approximately 300 ng / ml, approximately 310 ng / ml, approximately 320 ng / ml, approximately 330 ng / ml, approximately 340 ng / ml, approximately 350 ng / ml, approximately 360 ng / ml, approximately 370 ng / ml, approximately 380 ng / ml, approximately 390 ng / ml, approximately 400 ng / ml, approximately 410 ng / ml, approximately 420 ng / ml, approximately 430 ng / ml, approximately 440 ng / ml, approximately 450 ng / ml Approximately 460 ng / mL, approximately 470 ng / mL, approximately 480 ng / mL, approximately 490 ng / mL, approximately 500 ng / mL, approximately 510 ng / mL, approximately 520 ng / mL, approximately 530 ng / mL, approximately 540 ng / mL, approximately 550 ng / mL, approximately 560 ng / mL, approximately 570 ng / mL, approximately 580 ng / mL, approximately 590 ng / mL, and approximately 600 ng / mL, including all values ​​and ranges therebetween. In some embodiments, the method described in this disclosure provides plasma Cmax of amotriptan at approximately 52 ng / mL to approximately 55 ng / mL.

[0115] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering a therapeutically effective amount of furostrecan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need amounts of furostrecan or a pharmaceutically acceptable salt thereof in the following quantities: about 1.0 mg to about 200 mg, including about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, etc. Approximately 7.5 mg, approximately 8.0 mg, approximately 8.5 mg, approximately 9.0 mg, approximately 9.5 mg, approximately 10.0 mg, approximately 10.5 mg, approximately 11.0 mg, approximately 11.5 mg, approximately 12.0 mg, approximately 12.5 mg, approximately 13.0 mg, approximately 13.5 mg, approximately 14.0 mg, approximately 14.5 mg, approximately 15.0 mg, approximately 15.5 mg, approximately 16.0 mg, approximately 16.5 mg, approximately 17. 0mg, approximately 17.5mg, approximately 18.0mg, approximately 18.5mg, approximately 19.0mg, approximately 19.5mg, approximately 20.0mg, approximately 25mg, approximately 30mg, approximately 35mg, approximately 40mg, approximately 45mg, approximately 50mg, approximately 55mg, approximately 60mg, approximately 65mg, approximately 70mg, approximately 75mg, approximately 80mg, approximately 85mg, approximately 90mg, approximately 95mg, approximately 100mg, approximately 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, and about 200 mg, including all values ​​and ranges therein. In some embodiments, about 11 mg to about 193 mg of furotriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 2 mg to about 7.5 mg of furotriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0116] In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of furostrecan or a pharmaceutically acceptable salt thereof: about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, about 11.0 mg, about 11.5 mg, about 12.0 mg, about 12.5 mg, about 13.0 mg, about 13.5 mg, about 14.0 mg, about 14.5 mg, about 15.0 mg, about 15.5 mg, about 16.0 mg, about 16.5 mg, about 17. 0mg, approximately 17.5mg, approximately 18.0mg, approximately 18.5mg, approximately 19.0mg, approximately 19.5mg, approximately 20.0mg, approximately 25mg, approximately 30mg, approximately 35mg, approximately 40mg, approximately 45mg, approximately 50mg, approximately 55mg, approximately 60mg, approximately 65mg, approximately 70mg, approximately 75mg, approximately 80mg, approximately 85mg, approximately 90mg, approximately 95mg, approximately 1 Approximately 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 195 mg, or 200 mg. In some embodiments, approximately 2.5 mg of furostrecan or a pharmaceutically acceptable salt thereof is administered to a patient in need.

[0117] In some implementations, furotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need once daily. In some implementations, furotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need twice daily. In some implementations, furotriptan or a pharmaceutically acceptable salt thereof is administered to patients in need three times daily.

[0118] In some embodiments, about 2.5 mg of furotriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 2.5 mg of furotriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 2.5 mg of furotriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 2.5 mg of furotriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0119] In some embodiments, the methods of this disclosure provide plasma levels of furoplastin (e.g., mean steady-state plasma levels) that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of furoplastin provided by the methods of this disclosure range from about 2 ng / mL to about 60 ng / mL, including about 2 ng / mL, about 2.5 ng / mL, about 3 ng / mL, about 3.5 ng / mL, about 4 ng / mL, about 4.5 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 15 ng / mL, 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, and about 60 ng / mL, including all values ​​and ranges therein.

[0120] In some embodiments, the method of this disclosure provides furotriptan with the following plasma Cmax: from about 2 ng / mL to about 60 ng / mL, including about 2 ng / mL, about 2.5 ng / mL, about 3 ng / mL, about 3.5 ng / mL, about 4 ng / mL, about 4.5 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 15 ng / mL, 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, and about 60 ng / mL, including all values ​​and ranges therebetween. In some embodiments, the method of this disclosure provides furotriptan with a plasma Cmax of about 2.5 ng / mL.

[0121] In some embodiments, the method of treating autism-related symptoms according to this disclosure includes administering a therapeutically effective amount of eletriptan or a pharmaceutically acceptable salt thereof to a patient in need. In some embodiments, the method includes administering to a patient in need an amount of eletriptan of the following amounts: about 10 mg to about 250 mg, including about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg. g, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, and about 250 mg, including all values ​​and ranges therein. In some embodiments, about 13 mg to about 235 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 20 mg to about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, about 20 mg to about 80 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to a patient in need. In some embodiments, the method described in this disclosure includes administering to a patient in need the following amounts of eletriptan or a pharmaceutically acceptable salt: about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg. Approximately 120 mg, approximately 125 mg, approximately 130 mg, approximately 135 mg, approximately 140 mg, approximately 145 mg, approximately 150 mg, approximately 155 mg, approximately 160 mg, approximately 165 mg, approximately 170 mg, approximately 175 mg, approximately 180 mg, approximately 185 mg, approximately 190 mg, approximately 195 mg, approximately 200 mg, approximately 205 mg, approximately 210 mg, approximately 215 mg, approximately 220 mg, approximately 225 mg, approximately 230 mg, approximately 235 mg, approximately 240 mg, or approximately 250 mg. In some embodiments, approximately 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to the patient in need.In some implementations, approximately 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered to patients in need.

[0122] In some implementations, eletriptan or a pharmaceutically acceptable salt thereof is administered to patients in need once daily. In some implementations, eletriptan or a pharmaceutically acceptable salt thereof is administered to patients in need twice daily. In some implementations, eletriptan or a pharmaceutically acceptable salt thereof is administered to patients in need three times daily.

[0123] In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 20 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0124] In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered once daily. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered twice daily. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered three times daily. In some embodiments, about 40 mg of eletriptan or a pharmaceutically acceptable salt thereof is administered four times daily.

[0125] In some embodiments, the methods of this disclosure provide plasma levels of eletriptan (e.g., mean steady-state plasma levels) that are correlated with one or more statistically significant therapeutic effects. In some embodiments, the therapeutically effective plasma levels of eletricane provided by the methods of this disclosure range from about 40 ng / mL to about 1200 ng / mL, including about 40 ng / mL, about 60 ng / mL, about 80 ng / mL, about 100 ng / mL, about 120 ng / mL, about 140 ng / mL, about 160 ng / mL, about 180 ng / mL, about 200 ng / mL, about 220 ng / mL, about 240 ng / mL, about 260 ng / mL, about 280 ng / mL, about 300 ng / mL, about 320 ng / mL, about 340 ng / mL, about 360 ng / mL, about 380 ng / mL, about 400 ng / mL, about 420 ng / mL, about 440 ng / mL, about 460 ng / mL, about 480 ng / mL, about 500 ng / mL, and about 520 ng / mL. g / ml, approximately 540 ng / ml, approximately 560 ng / ml, approximately 580 ng / ml, approximately 600 ng / mL, approximately 620 ng / ml, approximately 640 ng / ml, approximately 660 ng / ml, approximately 680 ng / ml, approximately 700 ng / ml, approximately 720 ng / ml, approximately 740 ng / ml, approximately 760 ng / ml, approximately 780 ng / ml, approximately 800 ng / ml, approximately 820 ng / ml, approximately 840 ng / ml, approximately 860 ng / ml, approximately 880 ng / ml, approximately 900 ng / ml, approximately 920 ng / ml, approximately 940 ng / ml, approximately 960 ng / ml, approximately 980 ng / ml, approximately 1000 ng / ml, approximately 1050 ng / mL, approximately 1100 ng / ml, approximately 1150 ng / mL, and approximately 1200 ng / mL, including all values ​​and ranges therein.

[0126] In some embodiments, the method of this disclosure provides eletricane with the following plasma Cmax: from about 40 ng / mL to about 1200 ng / mL, including about 40 ng / mL, about 60 ng / mL, about 80 ng / mL, about 100 ng / mL, about 120 ng / mL, about 140 ng / mL, about 160 ng / mL, about 180 ng / mL, about 200 ng / mL, about 220 ng / mL, about 240 ng / mL, about 260 ng / mL, about 280 ng / mL, about 300 ng / mL, about 320 ng / mL, about 340 ng / mL, about 360 ng / mL, about 380 ng / mL, about 400 ng / mL, about 420 ng / mL, about 440 ng / mL, about 460 ng / mL, about 480 ng / mL, about 500 ng / mL, about 520 ng / mL. The values ​​are approximately 540 ng / ml, 560 ng / ml, 580 ng / ml, 600 ng / mL, 620 ng / ml, 640 ng / ml, 660 ng / ml, 680 ng / ml, 700 ng / ml, 720 ng / ml, 740 ng / ml, 760 ng / ml, 780 ng / ml, 800 ng / ml, 820 ng / ml, 840 ng / ml, 860 ng / ml, 880 ng / ml, 900 ng / ml, 920 ng / ml, 940 ng / ml, 960 ng / ml, 980 ng / ml, 1000 ng / ml, 1050 ng / mL, 1100 ng / ml, 1150 ng / mL, and 1200 ng / mL, including all values ​​and ranges therein. In some embodiments, the methods of this disclosure provide plasma Cmax of eletriptan at about 45 ng / mL to about 210 ng / mL. In some embodiments, the methods of this disclosure provide plasma Cmax of eletriptan at about 46.5 ng / mL, about 94.5 ng / mL, or about 200 ng / mL.

[0127] In some implementations, triptans are administered once or more daily. In some implementations, triptans are administered once daily. In some implementations, triptans are administered twice daily. In some implementations, triptans are administered three times daily. In some implementations, triptans are administered more than three times daily.

[0128] In some embodiments, this disclosure provides a method for treating autism-related irritability, the method comprising administering a therapeutically effective amount of a triptan. In some embodiments, this disclosure provides a method for treating autism-related aggression, the method comprising administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof. In some embodiments, this disclosure provides a method for treating autism-related somnolence, the method comprising administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof. In some embodiments, this disclosure provides a method for treating autism-related social competence symptoms, the method comprising administering an effective amount of a triptan to improve socialization. In some embodiments, this disclosure provides a method for reducing autism-related social deficits, the method comprising administering an effective amount of a triptan or a pharmaceutically acceptable salt thereof.

[0129] In some implementations, patients experience a significant reduction in ASD-related symptoms (e.g., social symptoms, aggression, or irritability) after treatment, compared to before treatment. Non-limiting examples of ASD symptoms include irritability, difficulty communicating, difficulty socially interacting, compulsive interests, repetitive behaviors, inappropriate social interactions, lack of eye contact, compulsive behaviors, impulsivity, repetitive movements, self-harm, persistent repetitive speech or actions, learning disabilities, speech delay, intense interest in a limited number of things, attention problems, lack of awareness of others' emotions, depression, anxiety, voice changes, auditory sensitivity, and tics. In some implementations, patients in need experience a significant reduction in ASD-related irritability compared to before treatment. In some implementations, patients in need experience a significant improvement in social skills compared to before treatment. In some implementations, patients in need experience a significant reduction in ASD-related aggression compared to before treatment.

[0130] The Vinland Adaptive Behavior Inventory (VABS), 3rd Edition, is a standardized measure of adaptive behavior that assesses an individual's personal and social skills from birth to adulthood. Individuals can be assessed by teachers or caregivers using the VABS scale. According to the VABS, individuals are assigned a VABS Composite Adaptive Behavior Score, which measures their functioning compared to other individuals of the same age. Individuals are also assigned domain scores in communication, daily living skills, socialization, and motor skills to assess their strengths and weaknesses in adaptive behavior. For each domain score and the VABS Composite Adaptive Behavior Score, individuals receive a score from 20 to 140. Scores of 20 to 70 represent low adaptation. Scores of 71 to 85 represent moderately low adaptation. Scores of 86 to 114 represent moderately adequate adaptation. Scores of 115 to 129 represent moderately high adaptation. Scores of 130 to 140 represent high adaptation.

[0131] In some implementations, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by an increase of at least one point in the VABS adaptive behavior composite score compared to before treatment. In some implementations, the VABS adaptive behavior score increases by approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 points compared to before treatment. Approximately 34 points, approximately 35 points, approximately 36 points, approximately 37 points, approximately 38 points, approximately 39 points, approximately 40 points, approximately 41 points, approximately 42 points, approximately 43 points, approximately 44 points, approximately 45 points, approximately 46 points, approximately 47 points, approximately 48 points, approximately 49 points, approximately 50 points, approximately 51 points, approximately 52 points, approximately 53 points, approximately 54 points, approximately 55 points, approximately 56 points, approximately 57 points, approximately 58 points, approximately 59 points, approximately 60 points, approximately 61 points, approximately 62 points, approximately 63 points, approximately 64 points, approximately 65 points, approximately 66 points, approximately 67 points, approximately 68 points, approximately 69 points, or approximately 70 points.

[0132] In some implementations, the VABS adaptive behavior composite score increases by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, or at least about 60% compared to before the treatment.

[0133] In some implementations, after the treatment, the patient experiences an improvement in social competence, characterized by an increase in VABS adaptive behavior socialization domain scores compared to before treatment. In some implementations, the VABS adaptive behavior socialization domain scores increase by approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or approximately 3 points compared to before treatment. 3 points, approximately 34 points, approximately 35 points, approximately 36 points, approximately 37 points, approximately 38 points, approximately 39 points, approximately 40 points, approximately 41 points, approximately 42 points, approximately 43 points, approximately 44 points, approximately 45 points, approximately 46 points, approximately 47 points, approximately 48 points, approximately 49 points, approximately 50 points, approximately 51 points, approximately 52 points, approximately 53 points, approximately 54 points, approximately 55 points, approximately 56 points, approximately 57 points, approximately 58 points, approximately 59 points, approximately 60 points, approximately 61 points, approximately 62 points, approximately 63 points, approximately 64 points, approximately 65 points, approximately 66 points, approximately 67 points, approximately 68 points, approximately 69 points, or approximately 70 points.

[0134] In some embodiments, compared to pre-treatment levels, VABS adaptive behavior socialization domain scores increase by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, or at least about 60%. In some embodiments, patients experience at least a 10% improvement in VABS socialization domain scores after treatment. In some embodiments, patients experience at least a 35% improvement in VABS socialization domain scores after treatment.

[0135] In some implementations, following the treatment, patients experience improved communication, characterized by an increase in VABS adaptive behavior communication scores compared to pre-treatment levels. In some implementations, the increase in VABS adaptive behavior communication scores is approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 points compared to pre-treatment levels. Approximately 34 points, approximately 35 points, approximately 36 points, approximately 37 points, approximately 38 points, approximately 39 points, approximately 40 points, approximately 41 points, approximately 42 points, approximately 43 points, approximately 44 points, approximately 45 points, approximately 46 points, approximately 47 points, approximately 48 points, approximately 49 points, approximately 50 points, approximately 51 points, approximately 52 points, approximately 53 points, approximately 54 points, approximately 55 points, approximately 56 points, approximately 57 points, approximately 58 points, approximately 59 points, approximately 60 points, approximately 61 points, approximately 62 points, approximately 63 points, approximately 64 points, approximately 65 points, approximately 66 points, approximately 67 points, approximately 68 points, approximately 69 points, or approximately 70 points.

[0136] In some implementations, the VABS adaptive behavior communication domain score increases by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, or at least about 60% compared to before the treatment.

[0137] The Diagnostic Observational Scale for Autism, Version 2 (ADOS-2) is a tool that allows for accurate assessment and diagnosis of ASD across age, developmental level, and language skills. ADOS-2 is a clinician-managed observational assessment that comprises two behavioral domains: Social Influence (SA) and Restricted and Repetitive Behaviors (RRB). Individuals are administered one of five ADOS-2 modules, selected based on their expressive language level and chronological age. The Infant Module is for children between 12 and 30 months of age who do not consistently use phrases. Module 1 is for children 31 months and older who do not consistently use phrases. Module 2 is for children of any age who use phrases but are not verbally fluent. Module 3 is for verbally fluent children and younger adolescents. Module 4 is for verbally fluent older adolescents and adults. Individuals are assigned an ADOS-2 composite score ranging from 1 to 10. Individuals with ASD are characterized by an ADOS-2 composite score between 6 and 10.

[0138] In some implementations, compared to pre-treatment levels, patients experience a reduction in ASD-related symptoms associated with a decrease of at least one point in the ADOS-2 composite score. In some implementations, the improvement in ASD symptoms is characterized by a decrease of at least one, two, three, four, or five points in the ADOS-2 composite score compared to pre-treatment levels.

[0139] In some implementations, the patient experiences improvement in ASD symptoms, characterized by an improvement in the ADOS-2 composite score of at least about 5%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90% compared to before the treatment.

[0140] In some implementations, patients experience a reduction in ASD-related symptoms, characterized by a decrease of at least one point in their ADOS-2 Module 4 social impact score compared to pre-treatment levels. In some implementations, the decrease in ADOS-2 Module 4 social impact score is correlated with an improvement in social competence. In some implementations, the improvement in social competence is characterized by a decrease of at least one, two, three, four, five, or six points in their ADOS-2 Module 4 social impact score compared to pre-treatment levels.

[0141] In some embodiments, the improvement in social competence is characterized by a reduction of at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55% compared to before treatment. In some embodiments, the patient experiences an improvement in social competence, characterized by a reduction of at least 10% in the social interaction score according to the Autism Diagnosis Observation Scale Module 4 compared to before treatment.

[0142] Clinicians use the Clinical Global Impression-Severity (CGI-S) scale to assess the severity of symptoms in patients with ASD. Individuals are assigned a score from 1 to 7. A score of 1 represents a normal patient. A score of 7 represents the score of a patient with ASD.

[0143] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the CGI-S score of at least one point compared to before the treatment. In some embodiments, the patient experiences a decrease in the CGI-S scale score of at least one, at least two, at least three, at least four, or at least five points compared to before the treatment.

[0144] In some implementations, compared to before the treatment, the patient experiences a reduction in the CGI-S scale of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%.

[0145] Clinicians use the Clinical Global Impression-Severity (CGI-C) scale to assess changes in symptoms in patients with ASD. Individuals are assigned scores from 1 (very improved) to 7 (very bad).

[0146] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease of at least one point on the CGI-C scale. In some embodiments, the patient experiences an improvement in irritability, characterized by a CGI-C score ≤1, ≤2, ≤3, or ≤4 after the treatment. In some embodiments, the improvement in irritability is characterized by a Clinical Global Impression-Change (CGI-C) score ≤3 after the treatment. In some embodiments, the patient experiences an improvement in social competence, characterized by a CGI-C score ≤1, ≤2, ≤3, or ≤4 after the treatment. In some embodiments, the patient experiences an improvement in social competence, characterized by a CGI-C score ≤3 after the treatment.

[0147] The Autism Behavior Inventory (ABI) Social Deficit Subscale is a measure of changes in core and associated symptoms of ASD. Individuals are given either the full ABI (93 items) or the abbreviated ABI (36 items). Individuals are rated on a scale of 0 to 6 for each item, where 0 represents the absence of symptoms and 6 represents the most severe symptom. Individuals who score 0 do not exhibit symptoms. Individuals assigned a score of 6 experience severe ASD symptoms.

[0148] In some implementations, the patient experiences symptom improvement, characterized by a reduction in ABI score of at least one point. In some implementations, the patient experiences symptom improvement, characterized by a reduction in ABI score of at least one, at least two, at least three, or at least four points compared to before the treatment.

[0149] In some implementations, the patient experiences symptom improvement, characterized by a reduction in ABI score of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% compared to before the treatment.

[0150] Children aged two years and older are identified with ASD using the Childhood Autism Rating Scale (CARS). The CARS consists of 14 domains assessing behaviors associated with ASD and a 15th domain assessing a general impression of autism. Each domain is rated on a scale from one to four; higher scores are associated with a higher level of impairment. The total score ranges from low 15 to high 60; a score below 30 indicates a non-autistic individual, a score between 30 and 36.5 indicates mild to moderate autism, and a score between 37 and 60 indicates severe autism.

[0151] In some implementations, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the CARS total score of approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 points compared to before the treatment.

[0152] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the total CARS score of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% compared to before the treatment.

[0153] Effective quantitative measures of various dimensions of interpersonal behavior, communication, and repetitive / stereotyped behaviors associated with ASD were obtained using the Social Responsiveness Scale, Version 2 (SRS-2). Individuals were assigned a total t-score based on the SRS-2 proxy version. Individuals were also assigned a proxy t-score, which reflects the sum of responses to 65 questions on the Social Responsiveness Scale and is used as an index of the severity of social skills on the autism spectrum. Individuals achieving a proxy t-score greater than 76 were assigned a severe clinical diagnosis of ASD. If an individual was assigned a proxy t-score between 66 and 75, this was associated with a moderate lack of clinically significant reciprocal social behavior that causes significant interference with daily social interactions. If an individual was assigned a proxy t-score between 60 and 65, the individual exhibited mild to moderate deficits in social interactions. If a patient exhibited a proxy t-score of 59 or less, the patient exhibited normal social interactions.

[0154] In some implementations, patients in need exhibit a proxy total t-score of ≥66 before being given a therapeutically effective dose of triptans.

[0155] In some implementations, the patient experiences symptom improvement, characterized by a reduction in the total t-score of the proxy version by at least one point, or at least two points, or at least three points, or at least four points, or at least five points, or at least six points, or at least seven points, or at least eight points, or at least nine points, or at least ten points, or at least eleven points, or at least twelve points, or at least thirteen points, or at least fourteen points, or at least fifteen points, or at least sixteen points, or at least seventeen points, or at least eighteen points, or at least twenty points, or at least twenty-one points, or at least twenty-two points, or at least twenty-three points, or at least twenty-four points, or at least twenty-five points compared to before the treatment.

[0156] In some implementations, patients experience symptom improvement characterized by a reduction in the total t-score of the surrogate version of SRS-2 by at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% compared to before treatment.

[0157] The Social Responsiveness Scale for Adults (SRS-A) is a tool for assessing social responsiveness in adults. The SRS-A contains 65 items, rated from 0 to 3. A score of 0 indicates no symptoms. A score of 3 indicates severe symptoms. A total SRS-A score of 67 indicates that an individual has ASD. The maximum total SRS-A score is 195.

[0158] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in SRS-A score of at least one point compared to before treatment. In some embodiments, the patient experiences an improvement in social competence, characterized by a decrease in SRS-A score of at least one point. In some embodiments, after the treatment, the patient's SRS-A score decreases by approximately 1 point, or approximately 5 points, or approximately 10 points, or approximately 15 points, or approximately 20 points, or approximately 25 points, or approximately 30 points, or approximately 35 points.

[0159] In some embodiments, after the treatment, the patient exhibits a reduction in ASD-related symptoms, characterized by a decrease in SRS-A score of approximately 5%, approximately 10%, approximately 15%, approximately 20%, approximately 25%, approximately 30%, approximately 35%, approximately 40%, approximately 45%, approximately 50%, approximately 55%, approximately 60%, approximately 65%, or approximately 70% compared to before the treatment. In some embodiments, after the treatment, the patient exhibits a reduction in ASD-related symptoms, characterized by a decrease in SRS-A score of at least 10% compared to before the treatment.

[0160] In some implementations, improvements in social competence compared to pre-treatment levels are associated with reductions in SRS-A scores of approximately 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50%.

[0161] The Abnormal Behavior Checklist (ABC) is a behavioral rating scale used to assess individuals using five subscales: (1) irritability, agitation, and crying; (2) lethargy and social withdrawal; (3) stereotyped behaviors; (4) hyperactivity and nonconformity; and (5) inappropriate speech. Individuals can be assessed using the ABC by any adult who knows them well. The ABC contains 58 items that are used to assess the five subscales. Each item in the 58 items is rated from 0 to 3. A score of 0 indicates the absence of symptoms. A score of 3 indicates that the individual is experiencing highly severe symptoms. The items within each subscale are summed to obtain the subscale score. Possible subscale scores using the ABC range from 0 to 48, with higher scores indicating behavioral disorders.

[0162] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease of at least one point in the ABC Irritability, Agitation, and Crying (ABC-I) sub-score. In some embodiments, after the treatment, the patient experiences a reduction in irritability, characterized by a decrease in the ABC-I communication domain score compared to before the treatment.

[0163] In some implementation schemes, patients exhibit an ABC-I score of ≥18 prior to treatment.

[0164] In some embodiments, after the treatment, the patient experiences a reduction in irritability, characterized by a reduction of approximately 2, 4, 6, 8, 10, 15, 20, 25, or 30 points in the ABC-I domain scores compared to before the treatment. In some embodiments, compared to before the treatment, the ABC-I domain scores are reduced by approximately 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0165] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease of at least one point in the ABC-Somnolence and Social Withdrawal (ABC-LSW) sub-scores compared to before the treatment. In some embodiments, after the treatment, the patient experiences a reduction in somnolence and social withdrawal, characterized by a decrease in the ABC-LSW communication domain score compared to before the treatment.

[0166] In some implementations, the ABC-LSW communication domain score decreased by approximately 2, 4, 6, 8, 10, 15, 20, 25, or 30 points compared to before the treatment.

[0167] In some implementations, the ABC-LSW communication domain score decreased by approximately 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% compared to pre-treatment levels.

[0168] The Social Communication Questionnaire is a tool used by doctors to screen patients with ASD. Individuals' caregivers rate speaking individuals on a scale of 0 to 39, or non-speaking individuals on a scale of 0 to 33. Individuals with ASD are characterized by a Social Communication Questionnaire score exceeding 15.

[0169] In some implementations, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a reduction in the social communication questionnaire score of at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% compared to before the treatment.

[0170] The efficacy of treatment for ASD was evaluated using the Pervasive Developmental Disorders Behavior Inventory (PDDBI). The PDDBI assesses both problem behaviors and appropriate social, language, and learning / memory skills. The PDDBI is divided into two behavioral dimensions: (a) Approach-Withdrawal Problems, assessing maladaptive behaviors; and (b) Acceptance / Expressive Social Communication Competence, assessing social communication competence. The Approach-Withdrawal Problems dimension is further divided into behavioral domains, including Sensory / Perceptual Approach Behavior, Ritualistic / Resistant Binding (RITUAL), Sociopragmatic Problems (SOCPP), Semantic / Pragmatic Problems (SEMPP), Arousal Adjustment Problems (AROUSE), FEARS, and Aggression (AGG). The Acceptance / Expressive Social Communication Competence (REXSCA) dimension, assessing social communication competence, is further divided into behavioral domains, including Social Approach Behavior (SOCAPP), Expressive Language (EXPRESS), and Learning / Memory and Sensitive Language (LMRL). Individuals received a T-score and a composite score for each domain, the latter being the sum of the scores for each domain. Individuals with ASD were assigned a T-score greater than 50.

[0171] In some embodiments, the reduction in ASD-related symptoms provided by the methods of this disclosure is characterized using the Pervasive Developmental Disorders Behavioral Questionnaire (PDDBI). In some embodiments, the patient exhibits a T score greater than 50 prior to the treatment. In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a PDDBI reduction of approximately 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% compared to before the treatment.

[0172] The ATEC is a scale used to evaluate the effectiveness of ASD treatment. The ATEC is a one-page form designed to be completed by a parent, teacher, or caregiver. The ATEC consists of four subtests: verbal / language communication, social skills, sensory / cognitive awareness, and health / physical / behavioral health. Individuals are assigned ratings from 0 to 28 on the verbal / language communication subtest. Individuals are assigned ratings from 0 to 40 on the social skills subtest. Individuals are assigned ratings from 0 to 36 on the sensory / cognitive awareness subtest. Individuals are assigned ratings from 0 to 75 on the health / physical / behavioral health subtest. The scores of each subset are summed, and individuals may receive a maximum score of 180.

[0173] In some embodiments, after the treatment, patients experience a reduction in ASD-related symptoms, characterized by a decrease in average ATEC scores compared to before treatment. In some embodiments, after the treatment, patients experience improvements in verbal / language communication, characterized by a decrease in verbal / language communication subtest scores compared to before treatment. In some embodiments, after the treatment, patients experience improvements in social competence, characterized by a decrease in social competence subtest scores compared to before treatment. In some embodiments, after the treatment, patients experience improvements in sensory / cognitive awareness, characterized by a decrease in sensory / cognitive awareness subtest scores compared to before treatment. In some embodiments, after the treatment, patients experience improvements in health / physical / behavioral health, characterized by a decrease in health / physical / behavioral health ratings compared to before treatment.

[0174] In some implementations, compared to pre-treatment scores, patients exhibit a decrease of at least 1, approximately 2, approximately 3, approximately 4, approximately 5, approximately 6, approximately 7, approximately 8, approximately 9, approximately 10, approximately 11, approximately 12, approximately 13, approximately 14, approximately 15, approximately 16, approximately 17, approximately 18, approximately 19, or approximately 20 points in the ATEC social skills section. In some implementations, compared to pre-treatment scores, patients exhibit a decrease of at least 1 point in the ATEC social skills section.

[0175] In some embodiments, compared to pre-treatment levels, the patient exhibits a reduction of at least 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 50% in the ATEC social competence subclass. In some embodiments, compared to pre-treatment levels, the patient exhibits a reduction of at least 10% in the ATEC social competence subclass.

[0176] The reduction of ASD-related symptoms following administration of a therapeutically effective dose of triptans to patients in need is measured using goal-based / performance-based assessments. In some embodiments, the goal-based / performance-based assessment is selected from eye tracking of social stimuli (eye tracking), the Parental Engagement Assessment Questionnaire (JERI), and Noldus Ethovision analysis. In some embodiments, eye tracking of social stimuli is used to characterize the reduction of ASD-related symptoms provided by the methods of this disclosure. Patients with ASD exhibit significantly shorter fixation duration (eye contact) compared to their age-matched non-ASD peers. The more difficult it is for patients with ASD to locate and process relevant social information, the faster the stimulus is presented.

[0177] PCIT provides training methods designed to help adults improve their parenting and language skills and to help children learn how to better manage their emotions. In some implementations, Parent-Child Interaction Tasks (PCIT) are used to improve the relationship between caregivers and individuals with ASD. In some implementations, PCIT helps reduce behavioral problems in children and improve communication and interaction skills within the family. In some implementations, children participating in CPT develop greater self-esteem, experience less anger and frustration, see improvements in social, organizational, and play skills, feel safer and calmer, and communicate more effectively.

[0178] The Joint Engagement Ranking Inventory (JERI) is a tool used to measure early intervention goals for developmental disorders and delays such as ASD. The JERI is an 18-item questionnaire developed to measure relevant intervention goals such as non-participation, purposeful participation, joint participation, stereotyped, restricted, and repetitive behaviors, caregiver attention, initiation of communication, level and use of expressive language, reflective framing, following, caregiver influence, fluency and connectivity, and shared routines and rituals. Individuals assessed using the JERI scale scored from 1 to 7 on each item. A score of 7 was assigned to individuals with the most joint participation. A score of 1 was assigned to individuals with no joint participation events. Lower JERI scores were associated with ASD.

[0179] In some embodiments, the reduction of ASD symptoms is associated with a decrease in JERI scores compared to pre-treatment levels using the methods described in this disclosure. In some embodiments, after said treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in JERI scores compared to pre-treatment levels. In some embodiments, the JERI score decreases by approximately 10%, approximately 20%, approximately 30%, approximately 40%, approximately 50%, approximately 60%, or approximately 70% compared to pre-treatment levels.

[0180] The Ohio State University Autism Rating Scale-DSM-5 (OARS-5) measures persistent impairments in social interaction, restricted interests / activities, and repetitive behaviors, as well as the level of support from society, school, and community (Hollway, JA, Arnold, LE, and Aman, MG (September 2017). OSU Autism Rating Scale-DSM-5 (OARS-5).). The OARS-5 was developed to provide three types of aggregate scores: (A) a count of autism symptoms based on clinical interviews (OARS-5 total score); (b) a weighted average severity score based on the severity of autism symptoms derived from clinical interviews; and (c) an impairment index ranging from 0 to 9 based on the level of support required due to severity. The OARS-5 total score equals the OARS-5 Social Deficit Subscale score plus the OARS-5 Restricted Interest Patterns Subscale score.

[0181] OARS-5 includes the following component tables:

[0182] Part A: Persistent impairment in social interactions across multiple environments (OARS-5 Social Deficit Subscale score);

[0183] Part B: Restricted Interests / Activities and Repetitive Behavior Patterns (OARS-5 Restricted Interests Patterns Subscale Score) and

[0184] • Part C: Support level for Part A (social interaction / communication) and Part B (restricted and repetitive behaviors).

[0185] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the total OARS-5 score compared to before treatment. In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the total OARS-5 score of approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points compared to before treatment.

[0186] In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the OARS-5 social deficit subscale score compared to before treatment. In some embodiments, after the treatment, the patient experiences a reduction in ASD-related symptoms, characterized by a decrease in the OARS-5 social deficit subscale score of approximately 1, 2, 3, 4, 5, 6, 7, 8, or 9 points compared to before treatment.

[0187] In some implementations, following the treatment, patients experience a reduction in ASD-related symptoms, characterized by a decrease in the Ohio State University Clinical Global Impression of Autism (OSU Autism CGI) total score compared to before treatment. The OSU Autism CGI-S total score equals the sum of the OSU Autism CGI-Severity Scale (OSU Autism CGI-S) score and the OSU Autism CGI-I Improvement Scale (OSU Autism CGI-I) score.

[0188] In some implementations, after the treatment, the patient experiences a reduction in symptoms associated with ASD, characterized by a decrease in the OSU Autism CGI total score of approximately 1, 2, 3, 4, 5, 6, or 7 points compared to before treatment.

[0189] In some embodiments, following the treatment, patients experience a reduction in ASD-related symptoms, characterized by a decrease in the Ohio State University Clinical Global Impression-Improvement Scale (OSU Autism CGI-I) score compared to before treatment. In some embodiments, following the treatment, patients experience a reduction in ASD-related symptoms, characterized by a decrease in the OSU Autism CGI-I score of approximately 1, 2, 3, 4, 5, 6, or 7 points compared to before treatment.

[0190] In some embodiments, following the treatment, patients experience a reduction in ASD-related symptoms, characterized by a decrease in the Ohio State University Clinical Global Impression-Severity Scale (OSU Autism CGI-S) score compared to before treatment. In some embodiments, following the treatment, patients experience a reduction in ASD-related symptoms, characterized by a decrease in the OSU Autism CGI-S score of approximately 1, 2, 3, 4, 5, 6, or 7 points compared to before treatment.

[0191] patient group

[0192] In some implementations, this disclosure provides a method for treating symptoms associated with autism spectrum disorder (ASD), the method comprising administering a therapeutically effective amount of a triptan to a patient in need.

[0193] In some implementations, patients who need treatment for ASD are those diagnosed with ASD according to the DSM-5 diagnostic criteria.

[0194] In some implementations, prior to treatment according to the methods described in this disclosure, patients with ASD in need have a score of ≥70 on the Wechsler Short Form Intelligence Scale. -II full scale IQ score.

[0195] In some embodiments, this disclosure provides methods for treating ASD-related symptoms that are refractory to existing ASD treatments. In some embodiments, the ASD-related symptoms are treated with aripiprazole to treat refractory symptoms. In some embodiments, the ASD-related symptoms are treated with risperidone to treat refractory symptoms.

[0196] In some implementations, the treated ASD patients exhibit atypical sensory processing. Sensory processing refers to the ability to record, process, and organize sensory information and respond appropriately to environmental demands, manifested as hypersensitivity or hyposensitivity to stimuli. Patients with atypical sensory processing may experience aversion to the color, taste, smell, and / or texture of food or medication. In some implementations, atypical sensory processing manifests as non-adherence to medication in patients with need. In some implementations, the treated ASD patients refuse to swallow medication. In some implementations, the medication is a liquid formulation or a pill.

[0197] In some implementations, the ASD patients being treated are infants. In some implementations, the ASD patients being treated are children. In some implementations, the ASD patients being treated are adolescents. In some implementations, the ASD patients being treated are adults. In some implementations, the ASD patients being treated are elderly patients.

[0198] Example

[0199] This disclosure is further illustrated by referring to the following embodiments. However, it should be noted that these embodiments, like the above-described embodiments, are illustrative and should not be construed as limiting the scope of the invention in any way.

[0200] General Solution

[0201] In mouse pharmacokinetic studies, the plasma Cmax of zolmitriptan occurred at the first time point measured (i.e., Tmax occurred at 15 minutes). The Tmax of intraperitoneally administered naratriptan, rizatriptan, furotriptan, and eletriptan also occurred at 15 minutes (i.e., the first time point measured in those studies).

[0202] Example 1.

[0203] The effects of zolmitriptan on aggressive behavior were investigated in a mouse model.

[0204] The rodent resident-intruder assay (RI) has been used to monitor aggressive behavior associated with patterns of behavior exhibited during territorial establishment and defense (Miczek et al., 1984). Correspondingly, the RI assay has been used preclinically to study the effects of drugs on rodent aggression (Miczek et al., 2001). The RI assay typically relies on the interpretation and scoring of aggressive (resident animal) behavioral patterns, and may also include analysis of defensive (intruder animal) behavioral patterns.

[0205] Aggressive behavior was evaluated using unfamiliar, naive, age-matched "invading" C57BL / 6 mice introduced into the living cages of at least 8-week-old "resident" male BALB / c mice for 5 minutes of interaction. The resident mice were isolated for one week prior to testing for aggressive behavior, while the intruders were housed in groups of four per cage throughout the study. All mice were provided with food and water freely.

[0206] Following a one-week quarantine period, aggressive behavior was recorded daily (Monday-Friday) for up to two weeks using a front-facing camera to establish a stable baseline before evaluating drug efficacy. Interactions were scored using Borris open-source event logging software to rate the total number of attacks initiated by the intruder and the cumulative duration of those attacks. Single-player matches lasting longer than 60 seconds were stopped, and the intruder was subsequently removed from the intrusion cage. Furthermore, if the intruder exhibited aggressive behavior, recording was stopped and the intruder was removed from the intrusion cage.

[0207] The effects of 3 and 10 mg / kg zolmitriptan on challenge were evaluated using the BALB / c-C57BL / 6RI combination. Resident mice were treated with the vector for two consecutive days, then equilibrated for a two-group (3 and 10 mg / kg) crossover study. On day 3, n=10 mice were treated with 3 mg / kg zolmitriptan, and n=10 mice received 10 mg / kg zolmitriptan. The vector treatment continued for days 4 and 5, followed by the final crossover day on day 6. Pretreatment lasted 15 minutes, and the drug was delivered via intraperitoneal (ip) injection.

[0208] Results: As shown in Figures 1 and 2, BALB / c mice exhibited a reduction in the number and duration of attacks when treated with zolmitriptan. A significant dose-dependent effect of zolmitriptan treatment on the reduction of aggressive behavior was found after the completion of the crossover study (p < 0.05, paired t-test). Furthermore, zolmitriptan doses of 3 and 10 mg / kg did not affect the normal locomotor activity of the treated mice.

[0209] Example 2

[0210] The effect of zolmitriptan (10 mg / kg) on ​​aggressive behavior in CD-1 mice was evaluated using a rodent RI assay with the CD-1-C57BL / 6 combination, performed according to the protocol described in Example 1. Risperidone (0.3 mg / kg) was used as a comparative compound. As a crossover design, the time to attack was measured over a 5-minute time interval.

[0211] Zolmitriptan administered at 3 and 10 mg / kg (ip) produced Cmax values ​​of 5.40 and 34.42 ng / ml in the CSF of adult male CD-1 mice, respectively. N-Desmethylzolmitriptan (“NDMZ”, the major metabolite of zolmitriptan found in humans) was below the lower limit of quantitation in male CD-1 mice administered at 3 and 10 mg / kg (ip).

[0212] Results: As shown in Figure 3 (and the table below), CD-1 mice administered 10 mg / kg zolmitriptan showed a greater reduction in challenge time (s) compared to risperidone (0.03 mg / kg) and the mediator control.

[0213] deal with N Attack time (s) SEM Attack latency (s) SEM vehicle 25 32.65 4.219 4.705 1.524 Risperidone 0.03 mg / kg 25 <![CDATA[21.58 * ]]> 3.123 12.98 4.18 Zolmitriptan 10 mg / kg 25 <![CDATA[18.46 *** ]]> 3.028 13.54 5.520

[0214] Example 3.

[0215] This study investigated the role of zolmitriptan in a mouse model of autism spectrum disorder induced by valproic acid (Nicolini C et al., 2018 Exp. Neurol., 2018, 217-227; Bey AL and Jiang JH, Current Protocols in Pharmacology, 2014 Sep 1, 66:5.66.1-26). Specifically, social abilities were evaluated in male c57 / Bl6 mice previously exposed to valproic acid (VPA) via intraperitoneal administration of 500 mg / kg to the pregnant mother on day 13 of embryonic development.

[0216] In this study, zolmitriptan was dissolved in 10% (2-hydroxypropyl)-β-cyclodextrin in physiological saline and administered intraperitoneally (ip). Mice were placed in the testing chamber 15 minutes prior to administration. Behavioral recordings were taken using an automated video tracking system (NoldusEthoVision v14) and analyzed and plotted using GraphPad Prism software v8. Social competence was assessed over a 10-minute timeframe in a 3-chamber social interaction assay. Individual mice were scored on their social competence using the time (in seconds) spent in the Social Interaction Zone (SIZ) compared to the Empty Interaction Zone (EIZ) in front of juvenile new C57 / BL6 mice. The social competence index was calculated using the SIZ / EIZ ratio. Social interaction preference was calculated using (SIZ) / (SIZ+EIZ)*100. Simultaneous recordings were taken in up to four arenas for the social interaction assay. Paired and unpaired t-tests were used as statistical tests.

[0217] Zolmitriptan administered at 10 mg / kg (ip) produced a Cmax of 17.83 ng / ml in the CSF of adult male c57 / Bl6 mice (i.e., the Tg2576 background strain and the strain used for VPA treatment) at 15 min post-administration. NDMZ was below the lower limit of quantitation in the CSF of male c57 / Bl6 mice administered at 10 mg / kg (ip).

[0218] As shown in Figure 4, zolmitriptan administered at 10 mg / kg (ip) improved the social competence index of adult male c57 / Bl6 mice previously exposed to valproic acid (VPA). The improvement in social competence in zolmitriptan-treated mice was statistically significant compared to the vector-treated group.

[0219] Example 4

[0220] The safety, tolerability, and pharmacokinetic response of oral zolmitriptan were investigated in healthy adult volunteers after multiple escalation doses.

[0221] Zolmitriptan 2.5 mg per tablet or placebo tablet was administered three times daily (TID) for the up-adjustment, 7-day, and down-adjustment phases. Dosing regimens are described in Table 1.

[0222] Table 1

[0223]

[0224] Lumbar puncture was performed on each subject to determine the concentration of zolmitriptan in CSF. CSF samples were collected on day 5 of treatment in group 1, day 7 of treatment in groups 2 and 3, and day 8 of treatment in groups 4 and 5. CSF was collected 2 hours (+ / - 30 minutes) after the morning dose. CSF concentration was measured using a validated bioanalytical method.

[0225] Results: As shown in Figure 5, CSF levels in humans were present at a ratio of zolmitriptan:NDMZ = 1.0:0.75. Overall, zolmitriptan was safe and well-tolerated in all groups.

[0226] Example 5.

[0227] The effective human dose of zolmitriptan for treating ASD symptoms was estimated using a human PK study that correlated oral doses of zolmitriptan with CSF concentrations (Example 4, i.e., the dose of zolmitriptan administered with the CSF Cmax achieved), the effective CSF concentrations determined from a valproic acid mouse model of ASD (Example 3), and species-specific binding assay data (human and mouse).

[0228] Specifically, the 5-HT1b receptor occupancy and efficacy model measures the potency of zolmitriptan and NDMZ at 5-HT1b receptors and the zolmitriptan:NDMZ ratio in human CSF. The 5-HT1b receptor efficacy model is used to predict the activation levels (i.e., efficacy) of both zolmitriptan and NDMZ on 5-HT1b based on the concentration of zolmitriptan in CSF (Table 5, column 2). The range required to achieve effective CSF exposure in humans is calculated from this target zolmitriptan dose (Table 5, column 3). Those skilled in the art can apply similar methods to determine the effective dose of the triptans described herein for the treatment of ASD symptoms.

[0229] 35S-GTPγS binding assay

[0230] In this study, in vitro binding assays were performed to measure the affinity of zolmitriptan, its active metabolite NDMZ, eletriptan, naratriptan, and rizatriptan for rat and human 5-HT1B receptors.

[0231] Zolmitriptan, eletriptan, naratriptan, and rizatriptan were tested in duplicate at ten concentrations in a SPA-based 35S-GTPγS binding assay in cells expressing human 5-HT1b (h5-HT1b) receptor or rat recombinant 5-HT1b (r5-HT1b) receptor. EC50 values ​​are shown in Table 2.

[0232] Table 2. Functional Measurement

[0233] Triptans h5-HT1b EC50(nM) r5-HT1b EC50(nM) Zormitritan 4 33 Ilequtan 8.8 120 Naraqutan 1.2 7.4 Rizatrotan 38 210

[0234] All triptans exhibited lower apparent affinity (i.e., EC50) at the rat 5-HT1b receptor than at the human 5-HT1b receptor. In the case of zolmitriptan, the interspecies difference was 8.3-fold.

[0235] The mouse and rat orthologs of 5-HT1b are 98% identical. They differ by only two amino acids, both of which are conserved changes and have been removed from the agonist-binding pocket (i.e., mouse / rat E152D in intracellular loop 1 and mouse / rat M192V in extracellular loop 2).

[0236] Based on this data, the CSF level required for zolmitriptan to provide therapeutic effects in humans is approximately 8.3 times lower than the CSF level required to provide similar activity in mice.

[0237] Assuming the CSF value reflects the free drug concentration in the brain, the estimated effective Cmax CSF value can be expressed as:

[0238] CD-1 (mouse challenge model, Example 2); 3 mg / Kg (ip); CSF Cmax = 18.8 nM or EC36 (36% activity in GTPgS)

[0239] c57 / Bl6 (ASD mouse model, Example 3); 10 mg / kg (ip); CSF Cmax = 62 nM EC65 (65% activity in GTPgS)

[0240] Radioligand binding competition assay

[0241] The affinity of zolmitriptan, NDMZ (the active metabolite of zolmitriptan in humans), eletriptan, naratriptan, rizatriptan, and furotriptan for the human 5-HT1B receptor was evaluated in duplicate at ten concentrations using a radioligand binding competition assay with 3H-5-CT and recombinant human 5-HT1B receptors. The affinity of the tested compounds for the h5-HT1B receptor is shown in Table 3. Ki values ​​were derived from the IC50 values ​​using the Cheng-Prusoff equation.

[0242] Table 3. Combined determination

[0243] Test compounds Ki(nM) Zormitritan 3.34 NDMZ 1.18 Ilequtan 4.48 Naraqutan 0.95 Rizatrotan 23.4 Furotriptan 3.36

[0244] 5-HT1b receptor occupancy and efficacy model

[0245] Using classical receptor theory, receptor occupancy can be predicted when considering two ligands (i.e., entities):

[0246] When considering the fixed concentrations of both A and B, the total occupancy % = (occupancy % of A) + {[100% - (occupancy % of A)] x (occupancy % of B)}.

[0247] Given that the ratio of zolmitriptan to NDMZ in human CSF is 1.0:0.75 (Figure 5) and that NDMZ is 2.83 times more potent than zolmitriptan, a 5-HT1b occupancy model was constructed based on the above total occupancy % formula. The model was transformed into a prediction of the activation levels (i.e., efficacy) of both zolmitriptan and NDMZ for 5-HT1b based on the concentration of zolmitriptan in CSF, using the efficacy predicted by the Clark equation {efficacy = [L] / ([L] + Ki); [L] = ligand concentration} instead of occupancy.

[0248] Total efficacy % = {[Zormitriptan] / ([Zormitriptan] + Ki,Z)} +

[0249] (100-{[Zormitrine] / ([Zormitrine]+Ki,Z)}x{[NDMZ] / ([NDMZ]+Ki,N)}

[0250] Using the EC50 value of zolmitriptan measured in GTPgS assay, the 2.83-fold affinity of NMDZ for human 5-HT1b receptor, and the measured zolmitriptan:NDMZ ratio of 1.0:0.75, the total efficacy % of a series of zolmitriptan concentrations was calculated, and the predicted total efficacy % was fitted using the logistic equation.

[0251] Total efficacy % = 100 / (1+10^((LogEC50-[zomitriptan]))), and Log EC50 is calculated to be -8.963. The predicted concentration of zomitriptan in human CSF for 5-HT1b inducing 50% efficacy (i.e., EC50) with zomitriptan and NDMZ is 1.09 nM or 0.31 ng / ml.

[0252] Due to the combined effect of potent metabolites, the concentration of zolmitriptan required to achieve 50% total efficacy is 3.7 times that of zolmitriptan EC50.

[0253] The dose range of zolmitriptan required to achieve the predicted effective CSF concentration range in humans is shown in Table 4 within the 5-HT1b activity range.

[0254] Table 4.

[0255] active Zolmitriptan [CSF] Zolmitriptan human dosage (mg) EC20–EC80 0.078–1.24 ng / ml 1.25–35 EC25–EC75 0.103–0.93 ng / ml 1.7–30 EC30–EC70 0.135–0.713 ng / ml 2.25–20 EC35–EC65 0.167–0.577 ng / ml 3–15 EC40–EC60 0.207–0.465 ng / ml 5–12.5

[0256] Dosage prediction for other triptans

[0257] The CSF:plasma ratio of zolmitriptan exposure in humans was 3.0% (compared to 0.76% in mice). There is no evidence that other triptans exhibit this species-specific bias.

[0258] Dosage predictions can be made by correlating the 5-HT1b EC50 and mouse CSF Cmax of other triptans with zolmitriptan values ​​(Tables 3 and 5). Although other triptans are not considered to produce potent active metabolites (i.e., NMDZ) like zolmitriptan, the contribution of any potential active metabolites of other triptans can be determined using similar 5-HT1b receptor occupancy and efficacy models as those disclosed herein for zolmitriptan.

[0259] Table 5.

[0260]

[0261] By incorporating references

[0262] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated herein by reference in their entirety for all purposes. However, reference to any reference, article, publication, patent, patent publication, or patent application cited herein is not and should not be construed as an admission or suggestion of any kind that they constitute valid prior art or are part of common general knowledge in any country of the world.

[0263] Implementation Plan

[0264] 1. A method for treating symptoms associated with autism spectrum disorder (ASD), the method comprising administering a therapeutically effective amount of a triptan to a patient in need.

[0265] 2. The method according to implementation scheme 1, wherein prior to the treatment, the patient was diagnosed with ASD using the DSM-5 diagnostic criteria.

[0266] 3. The method according to any one of the embodiments 1-2, wherein prior to the treatment, the patient's score on the Irritability Subscale (ABC-I) of the Abnormal Behavior Checklist is ≥18.

[0267] 4. The method according to any one of embodiments 1-3, wherein prior to the treatment, the patient's total t-score on the Social Response Scale Version 2 (SRS-2) proxy version is ≥66.

[0268] 5. The method according to any one of embodiments 1-4, wherein prior to the treatment, the patient is assessed using the Wechsler Short Form Intelligence Scale. -II Full Scale IQ score ≥70.

[0269] 6. The method according to any one of embodiments 1-5, wherein prior to the treatment, the patient had severe irritability and / or aggression.

[0270] 7. The method according to any one of embodiments 1-6, wherein prior to the treatment, the patient had moderate irritability and / or aggression.

[0271] 8. The method according to any one of embodiments 1-7, wherein prior to the treatment, the patient had moderate somnolence and / or social deficits.

[0272] 9. The method according to any one of embodiments 1-8, wherein the patient's symptoms are refractory to treatment with aripiprazole and risperidone.

[0273] 10. The method according to any one of embodiments 1-9, wherein the patient is an adolescent.

[0274] 11. The method according to any one of embodiments 1-9, wherein the patient is a child.

[0275] 12. The method according to any one of embodiments 1-9, wherein the patient is an adult.

[0276] 13. The method according to any one of embodiments 1-12, wherein the triptan is selected from sumatriptan, zolmitriptan, naratriptan, rizatriptan, amotriptan, furotriptan, eletriptan, donitriptan, and avetriptan or a pharmaceutically acceptable salt thereof.

[0277] 14. The method according to any one of embodiments 1-13, wherein the triptan drug is administered orally.

[0278] 15. The method according to any one of embodiments 1-13, wherein the triptan drug is administered intranasally.

[0279] 16. The method according to any one of embodiments 1-13, wherein the triptan drug is administered subcutaneously.

[0280] 17. The method according to any one of embodiments 1-16, wherein the triptan drug is administered once daily.

[0281] 18. The method according to any one of embodiments 1-16, wherein the triptan drug is administered twice daily.

[0282] 19. The method according to any one of embodiments 1-16, wherein the triptan drug is administered three times daily.

[0283] 20. The method according to any one of embodiments 1-19, wherein the triptan is sumatriptan or a pharmaceutically acceptable salt thereof.

[0284] 21. The method according to any one of embodiments 1-20, wherein the triptan is sumatriptan hydrochloride.

[0285] 22. The method according to any one of embodiments 1-20, wherein the triptan is sumatriptan succinate.

[0286] 23. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 3 mg of sumatriptan is administered once daily.

[0287] 24. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 3 mg of sumatriptan is administered twice daily.

[0288] 25. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 3 mg of sumatriptan is administered three times daily.

[0289] 26. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 3 mg of sumatriptan is administered four times daily.

[0290] 27. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 6 mg of sumatriptan is administered once daily.

[0291] 28. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 6 mg of sumatriptan is administered twice daily.

[0292] 29. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 5 mg of sumatriptan is administered once daily.

[0293] 30. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 5 mg of sumatriptan is administered twice daily.

[0294] 31. The method according to any one of embodiments 1-16 and 20-22, wherein about 10 mg of sumatriptan is administered once daily.

[0295] 32. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 10 mg of sumatriptan is administered twice daily.

[0296] 33. The method according to any one of embodiments 1-16 and 20-22, wherein about 10 mg of sumatriptan is administered three times daily.

[0297] 34. The method according to any one of embodiments 1-16 and 20-22, wherein about 20 mg of sumatriptan is administered once daily.

[0298] 35. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 20 mg of sumatriptan is administered twice daily.

[0299] 36. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 22 mg of sumatriptan is administered once daily.

[0300] 37. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 22 mg of sumatriptan is administered twice daily.

[0301] 38. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 25 mg of sumatriptan is administered once daily.

[0302] 39. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 25 mg of sumatriptan is administered twice daily.

[0303] 40. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 50 mg of sumatriptan is administered once daily.

[0304] 41. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 50 mg of sumatriptan is administered twice daily.

[0305] 42. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 100 mg of sumatriptan is administered once daily.

[0306] 43. The method according to any one of embodiments 1-16 and 20-22, wherein approximately 100 mg of sumatriptan is administered twice daily.

[0307] 44. The method according to any one of embodiments 1-19, wherein the triptan is zolmitriptan or a pharmaceutically acceptable salt thereof.

[0308] 45. The method according to any one of embodiments 1-16 and 44, wherein about 1.25 mg of zolmitriptan is administered once daily.

[0309] 46. ​​The method according to any one of embodiments 1-16 and 44, wherein about 1.25 mg of zolmitriptan is administered twice daily.

[0310] 47. The method according to any one of embodiments 1-16 and 44, wherein about 1.25 mg of zolmitriptan is administered three times daily.

[0311] 48. The method according to any one of embodiments 1-16 and 44, wherein about 2.5 mg of zolmitriptan is administered once daily.

[0312] 49. The method according to any one of embodiments 1-16 and 44, wherein about 2.5 mg of zolmitriptan is administered twice daily.

[0313] 50. The method according to any one of embodiments 1-16 and 44, wherein about 2.5 mg of zolmitriptan is administered three times daily.

[0314] 51. The method according to any one of embodiments 1-16 and 44, wherein about 5 mg of zolmitriptan is administered once daily.

[0315] 52. The method according to any one of embodiments 1-16 and 44, wherein about 5 mg of zolmitriptan is administered twice daily.

[0316] 53. The method according to any one of embodiments 1-16 and 44, wherein about 5 mg of zolmitriptan is administered three times daily.

[0317] 54. The method according to any one of embodiments 1-16 and 44, wherein about 7.5 mg of zolmitriptan is administered once daily.

[0318] 55. The method according to any one of embodiments 1-16 and 44, wherein approximately 7.5 mg of zolmitriptan is administered twice daily.

[0319] 56. The method according to any one of embodiments 1-16 and 44, wherein about 7.5 mg of zolmitriptan is administered three times daily.

[0320] 57. The method according to any one of embodiments 1-16 and 44, wherein about 10 mg of zolmitriptan is administered once daily.

[0321] 58. The method according to any one of embodiments 1-16 and 44, wherein about 10 mg of zolmitriptan is administered twice daily.

[0322] 59. The method according to any one of embodiments 1-16 and 44, wherein about 10 mg of zolmitriptan is administered three times daily.

[0323] 59a. The method according to any one of embodiments 1-16 and 44, wherein about 12.5 mg of zolmitriptan is administered once daily.

[0324] 59b. The method according to any one of embodiments 1-16 and 44, wherein approximately 12.5 mg of zolmitriptan is administered twice daily.

[0325] 59c. The method according to any one of embodiments 1-16 and 44, wherein about 12.5 mg of zolmitriptan is administered three times daily.

[0326] 59d. The method according to any one of embodiments 1-16 and 44, wherein about 15 mg of zolmitriptan is administered once daily.

[0327] 59e. The method according to any one of embodiments 1-16 and 44, wherein about 15 mg of zolmitriptan is administered twice daily.

[0328] 59f. The method according to any one of embodiments 1-16 and 44, wherein about 15 mg of zolmitriptan is administered three times daily.

[0329] 59g. The method according to any one of embodiments 1-16 and 44, wherein approximately 17.5 mg of zolmitriptan is administered once daily.

[0330] 59h. The method according to any one of embodiments 1-16 and 44, wherein approximately 17.5 mg of zolmitriptan is administered twice daily.

[0331] 59i. The method according to any one of embodiments 1-16 and 44, wherein approximately 17.5 mg of zolmitriptan is administered three times daily.

[0332] 59j. The method according to any one of embodiments 1-16 and 44, wherein about 20 mg of zolmitriptan is administered once daily.

[0333] 59k. The method according to any one of embodiments 1-16 and 44, wherein about 20 mg of zolmitriptan is administered twice daily.

[0334] 59l. The method according to any one of embodiments 1-16 and 44, wherein about 20 mg of zolmitriptan is administered three times daily.

[0335] 59m. The method according to any one of embodiments 1-16 and 44, wherein about 25 mg of zolmitriptan is administered once daily.

[0336] 59n. The method according to any one of embodiments 1-16 and 44, wherein about 25 mg of zolmitriptan is administered twice daily.

[0337] 59o. The method according to any one of embodiments 1-16 and 44, wherein about 25 mg of zolmitriptan is administered three times daily.

[0338] 59p. The method according to any one of embodiments 1-16 and 44, wherein about 30 mg of zolmitriptan is administered once daily.

[0339] 59q. The method according to any one of embodiments 1-16 and 44, wherein about 30 mg of zolmitriptan is administered twice daily.

[0340] 59r. The method according to any one of embodiments 1-16 and 44, wherein about 30 mg of zolmitriptan is administered three times daily.

[0341] 59s. The method according to any one of embodiments 1-16 and 44, wherein about 35 mg of zolmitriptan is administered once daily.

[0342] 59t. The method according to any one of embodiments 1-16 and 44, wherein about 35 mg of zolmitriptan is administered twice daily.

[0343] 59u. The method according to any one of embodiments 1-16 and 44, wherein about 35 mg of zolmitriptan is administered three times daily.

[0344] 59v. The method according to any one of embodiments 1-16 and 44, wherein about 40 mg of zolmitriptan is administered once daily.

[0345] 59w. The method according to any one of embodiments 1-16 and 44, wherein about 40 mg of zolmitriptan is administered twice daily.

[0346] 59x. The method according to any one of embodiments 1-16 and 44, wherein about 40 mg of zolmitriptan is administered three times daily.

[0347] 59y. The method according to any one of embodiments 1-16 and 44, wherein about 45 mg of zolmitriptan is administered once daily.

[0348] 59z. The method according to any one of embodiments 1-16 and 44, wherein about 45 mg of zolmitriptan is administered twice daily.

[0349] 59a'. The method according to any one of embodiments 1-16 and 44, wherein about 45 mg of zolmitriptan is administered three times daily.

[0350] 60. The method according to any one of embodiments 1-19, wherein the triptan is naratriptan or a pharmaceutically acceptable salt thereof.

[0351] 61. The method according to any one of embodiments 1-19 and 60, wherein the triptan is naratriptan hydrochloride.

[0352] 62. The method according to any one of embodiments 1-16 and 60-61, wherein about 1 mg of natratriptan is administered once daily.

[0353] 63. The method according to any one of embodiments 1-16 and 60-62, wherein about 1 mg of natratriptan is administered twice daily.

[0354] 64. The method according to any one of embodiments 1-16 and 60-62, wherein about 2.5 mg of natratriptan is administered once daily.

[0355] 65. The method according to any one of embodiments 1-16 and 60-62, wherein about 2.5 mg of natratriptan is administered twice daily.

[0356] 66. The method according to any one of embodiments 1-19, wherein the triptan is rizatriptan or a pharmaceutically acceptable salt thereof.

[0357] 67. The method according to any one of embodiments 1-19 and 66, wherein the triptan is rizatriptan benzoate.

[0358] 68. The method according to any one of embodiments 1-16 and 66-67, wherein about 5 mg of rizatriptan is administered once daily.

[0359] 69. The method according to any one of embodiments 1-16 and 66-67, wherein about 5 mg of rizatriptan is administered twice daily.

[0360] 70. The method according to any one of embodiments 1-16 and 66-67, wherein about 10 mg of rizatriptan is administered once daily.

[0361] 71. The method according to any one of embodiments 1-16 and 66-67, wherein about 10 mg of rizatriptan is administered twice daily.

[0362] 72. The method according to any one of embodiments 1-16 and 66-67, wherein about 10 mg of rizatriptan is administered three times daily.

[0363] 73. The method according to any one of embodiments 1-19, wherein the triptan is amotriptan or a pharmaceutically acceptable salt thereof.

[0364] 74. The method according to any one of embodiments 1-19 and 73, wherein the triptan is amotriptan malate.

[0365] 75. The method according to any one of embodiments 1-16 and 73-74, wherein about 6.25 mg of amotriptan is administered once daily.

[0366] 76. The method according to any one of embodiments 1-16 and 73-74, wherein about 6.25 mg of amotriptan is administered twice daily.

[0367] 77. The method according to any one of embodiments 1-16 and 73-74, wherein about 12.5 mg of amotriptan is administered once daily.

[0368] 78. The method according to any one of embodiments 1-16 and 73-74, wherein about 12.5 mg of amotriptan is administered twice daily.

[0369] 79. The method according to any one of embodiments 1-19, wherein the triptan is furotriptan or a pharmaceutically acceptable salt thereof.

[0370] 80. The method according to any one of embodiments 1-19 and 79, wherein the triptan is furostretan succinate.

[0371] 81. The method according to any one of embodiments 1-16 and 79-80, wherein approximately 2.5 mg of furostretan is administered once daily.

[0372] 82. The method according to any one of embodiments 1-16 and 79-80, wherein approximately 2.5 mg of furostretan is administered twice daily.

[0373] 83. The method according to any one of embodiments 1-16 and 79-80, wherein about 2.5 mg of furostretan is administered three times daily.

[0374] 84. The method according to any one of embodiments 1-19, wherein the triptan is eletriptan or a pharmaceutically acceptable salt thereof.

[0375] 85. The method according to any one of embodiments 1-19 and 84, wherein the triptan is eletriptan hydrobromide.

[0376] 86. The method according to any one of embodiments 1-16 and 84-85, wherein about 20 mg of eletriptan is administered once daily.

[0377] 87. The method according to any one of embodiments 1-16 and 84-85, wherein about 20 mg of eletriptan is administered twice daily.

[0378] 88. The method according to any one of embodiments 1-16 and 84-85, wherein about 40 mg of eletriptan is administered once daily.

[0379] 89. The method according to any one of embodiments 1-16 and 84-85, wherein about 40 mg of eletriptan is administered twice daily.

[0380] 90. The method according to any one of embodiments 1-89, wherein after the treatment, the patient experiences a significant reduction in ASD-related symptoms compared to before the treatment.

[0381] 91. The method according to any one of embodiments 1-90, wherein after the treatment, the patient experiences a significant improvement in social abilities compared to before the treatment.

[0382] 92. The method according to any one of embodiments 1-91, wherein after the treatment, the patient experiences an improvement in social skills, characterized in that the social skills section of the Autism Treatment Evaluation Checklist (ATEC) is reduced by at least 1 point compared to before the treatment.

[0383] 93. The method according to any one of embodiments 1-92, wherein after the treatment, the patient experiences an improvement in social competence, characterized in that the social competence partition of ATEC is reduced by at least 10% compared with before the treatment.

[0384] 94. The method according to any one of embodiments 1-93, wherein after the treatment, the patient experiences an improvement in social competence, characterized in that the social interaction score of module 4 of the Autism Diagnosis Observation Scale decreases by at least 1 point compared with before the treatment.

[0385] 95. The method according to any one of embodiments 1-94, wherein after the treatment, the patient experiences an improvement in social competence, characterized in that the social interaction score of the Autism Diagnosis Observation Scale module 4 is reduced by at least 10% compared with before the treatment.

[0386] 96. The method according to any one of embodiments 1-95, wherein after the treatment, the patient experiences an improvement in social competence, characterized in that the Social Response Scale (SRS-A) score decreases by at least 1 point compared to before the treatment.

[0387] 97. The method according to any one of embodiments 1-96, wherein after the treatment, the patient experiences an improvement in social competence, characterized in that the SRS-A score is reduced by at least 10% compared to before the treatment.

[0388] 98. The method according to any one of embodiments 1-97, wherein after the treatment, the patient experiences an improvement in social competence related to ASD, characterized in that the Clinical Global Impression-Change (CGI-C) score is ≤3.

[0389] 99. The method according to any one of embodiments 1-98, wherein after the treatment, the patient experiences a significant reduction in ASD-related irritability compared to before the treatment.

[0390] 100. The method according to any one of embodiments 1-99, wherein after the treatment, the patient experiences an improvement in ASD-related irritability, characterized in that the ABC-I score is reduced by at least one point compared to before the treatment.

[0391] 101. The method according to any one of embodiments 1-100, wherein after the treatment, the patient experiences an improvement in ASD-related irritability, characterized in that the ABC-I score is reduced by at least 10% compared to before the treatment.

[0392] 102. The method according to any one of embodiments 1-101, wherein after the treatment, the patient experiences an improvement in ASD-related irritability, characterized in that the ABC-I score is reduced by at least 35% compared to before the treatment.

[0393] 103. The method according to any one of embodiments 1-102, wherein after the treatment, the patient experiences an improvement in irritability associated with ASD, characterized in that the Clinical Global Impression-Change (CGI-C) score is ≤3.

[0394] 104. The method according to any one of embodiments 1-103, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the socialization domain score of the Vinland 3 Adaptive Behavior Scale improves by at least 10% compared to before the treatment.

[0395] 105. The method according to any one of embodiments 1-104, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the socialization domain score of the Vinland 3 Adaptive Behavior Scale is improved by at least 35% compared to before the treatment.

[0396] 106. The method according to any one of embodiments 1-105, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the communication domain score of the Vinland 3 Adaptive Behavior Scale improves by at least 10% compared to before the treatment.

[0397] 107. The method according to any one of embodiments 1-106, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the communication domain score of the Vinland 3 Adaptive Behavior Scale is improved by at least 35% compared with before the treatment.

[0398] 108. The method according to any one of embodiments 1-107, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the overall total score of the Diagnostic Observational Scale for Autism Scale, Second Edition (ADOS-2) improves by at least one point compared to before the treatment.

[0399] 109. The method according to any one of embodiments 1-108, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the OARS-5 total score is reduced by at least one point compared to before the treatment.

[0400] 110. The method according to any one of embodiments 1-109, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the OARS-5 social deficit subscale score is reduced by at least one point compared to before the treatment.

[0401] 111. The method according to any one of embodiments 1-110, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the OSU autism CGI total score decreases by at least one point compared to before the treatment.

[0402] 112. The method according to any one of embodiments 1-111, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the OSU autism CGI-I score decreases by at least one point compared to before the treatment.

[0403] 113. The method according to any one of embodiments 1-111, wherein after the treatment, the patient experiences improvement in ASD symptoms, characterized in that the OSU autism CGI-S score decreases by at least one point compared to before the treatment.

Claims

1. Use in the preparation of a medicine for reducing irritability associated with autism spectrum disorder (ASD) or improving social competence associated with autism spectrum disorder (ASD) in patients in need.

2. The use according to claim 1, wherein prior to treatment, the patient was diagnosed with ASD using the DSM-5 diagnostic criteria, and wherein the drug is an oral medication.

3. The use according to claim 1, wherein prior to treatment, the patient's Irritability Subscale (ABC-I) score is ≥ 18, and wherein the drug is a tablet.

4. The use according to any one of claims 1-3, wherein the drug comprises 1 mg to 50 mg of zolmitriptan or a pharmaceutically acceptable salt thereof.

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