Lithium salts of n-substituted glycine compounds and uses thereof

Abstract

The present invention relates to a composition comprising a lithium salt of an N-substituted glycine compound and a carrier, wherein the lithium salt of the N-substituted glycine compound is of Formula (I):in which R1, R2, and R3 each are independently hydrogen, alkyl, alkenyl, alkynyl, aralkyl, carbocyclyl, aryl, or heteroaryl, or one of R1, R2, and R3 is absent. Also provided in the present invention is a method of mitigating at least one symptom of a neuropsychiatric disorder, comprising administering to a subject in need thereof the lithium salt of an N-substituted glycine compound of Formula (I).

1 - 25 . (canceled) 
     
     
         26 . A method for mitigating a symptom of a neuropsychiatric disorder, comprising administering to a subject in need thereof an effective amount of a lithium salt of an N-substituted glycine compound or a composition comprising the lithium salt,
 wherein the lithium salt of the N-substituted glycine compound is of Formula (Ia):   
       
         
           
           
               
               
           
         
       
       in which R 1 , R 2 , and R 3  each are independently alkyl, alkenyl, alkynyl, aralkyl, carbocyclyl, aryl, or heteroaryl; and
 wherein the neuropsychiatric disorder is a neuropsychiatric disorder having hyperactivity symptoms, sensorimotor deficit, and/or a deficit in learning and memory. 
 
     
     
         27 . The method of  claim 26 , wherein R 1 , R 2 , and R 3  each are independently alkyl, which is C 1-3  alkyl. 
     
     
         28 . The method of  claim 27 , wherein the C 1-3  alkyl at one or more of R 1 , R 2 , and R 3  is methyl. 
     
     
         29 . The method of  claim 28 , wherein R 1 , R 2 , and R 3  are each methyl. 
     
     
         30 . The method of  claim 26 , wherein the composition comprising the lithium salt is a pharmaceutical composition, a nutraceutical composition, a health food, or a medical food. 
     
     
         31 . The method of  claim 26 , wherein the neuropsychiatric disorder is selected from the group consisting of schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, tic disorder, obsessive compulsive disorder, Tourette's syndrome, blepharospasm, autism spectrum disorders, Asperger's disorder, Fragile X syndrome, Parkinson's disease, dementia, Huntington's disease, nocturnal enuresis, Duchenne muscular dystrophy, non-epileptic seizures, and amyotrophic lateral sclerosis 
     
     
         32 . The method of  claim 26 , wherein the subject is treated by an additional pharmaceutical agent for the neuropsychiatric disorder. 
     
     
         33 . The method of  claim 32 , wherein the additional pharmaceutical agent is selected from the group consisting of an antipsychotic, an anxiolytic, or a psychostimulant. 
     
     
         34 . The method of  claim 33 , wherein the additional pharmaceutical agent is an antipsychotic selected from the group consisting of butyrophenone, phenothiazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, promazine, triflupromazine, levomepromazine, promethazine, thioxanthene, chlorprothixene, flupentixol, thiothixene, zuclopenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, asenapine, paliperidone, aripiprazole, cannabidiol, LY2140023, droperidol, pimozide, butaperazine, carphenazine, remoxipride, piperacetazine, sulpiride, acamprosate, tannic acid, and tetrabenazine. 
     
     
         35 . The method of  claim 33 , wherein the additional pharmaceutical agent is a psychostimulant selected from the group consisting of methylphenidate, dextro-threo-methylphenidate, isopropylphenidate, cocaine, amphetamine, methamphetamine, dextroamphetamine, 3,4-methylenedioxymethamphetamine, pemoline, phenmetrazine, diethylpropion, chlorphentermine, pipradol, p-hydroxymorphedrine, fenfluramine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane, bupropion, statins, modafinil, arecoline, dexmethylphenidate, lisdexamfetamine dimesylate, mixed salts amphetamine, atomoxetine, clonidine hydrochloride, guanfacine hydrochloride, and arecoline. 
     
     
         36 . The method of  claim 33 , wherein the additional pharmaceutical agent is an anxiolytic selected from the group consisting of diazepam, alprazolam, triazolam, indiplon, zaleplon, bromazepam, oxazepam, buspirone, hydroxyzine, mecloqualone, medetomidine, metomidate, adinazolam, chlordiazepoxide, clobenzepam, flurazepam, lorazepam, clonazepam, loprazolam, midazolam, alpidem, alseroxlon, amphenidone, azacyclonol, bromisovalum, chlorazepate, calcium N-carboamoylaspartate, captodiamine, capuride, carbcloral, carbromal, chloral betaine, enciprazine, flesinoxan, ipsapiraone, ipsapirone, lesopitron, loxapine, methaqualone, methprylon, propanolol, tandospirone, trazadone, zopiclone, and zolpidem. 
     
     
         37 . The method of  claim 32 , wherein the disorder is Alzheimer's disease (AD) and the additional pharmaceutical agent is selected from the group consisting of donepezil, rivastigmine, galantamine, memantine, selfotel, midafotel, tacrine, selegiline, and vitamin E. 
     
     
         38 . The method of  claim 32 , wherein the additional pharmaceutical agent is administered prior to, concurrently with, or subsequent to the administration of the lithium salt of the N-substituted glycine compound. 
     
     
         39 . The method of  claim 26 , wherein the lithium salt of the N-substituted glycine compound is administered to the subject at about 50 mg/kg to about 300 mg/kg. 
     
     
         40 . The method of  claim 39 , wherein the lithium salt of the N-substituted glycine compound is administered to the subject at about 120 mg/kg to about 300 mg/kg. 
     
     
         41 . The method of  claim 39 , wherein the lithium salt of the N-substituted glycine compound is administered to the subject at about 50 mg/kg to about 120 mg/kg.