Anticonvulsive pharmaceutical compositions

Abstract

The use of substance selected from taurine, a taurine precursor, a taurine metabolite, a taurine derivative, a taurine analog and a substance required for the taurine biosynthesis, for preventing or inhibiting the undesirable side-effects caused to a human or an animal organism by an active ingredient that induces a high level of extracellular GABA or increases GABA receptor activation, and a pharmaceutical composition including the substance and the active ingredient.

1 . A pharmaceutical composition comprising, as the active ingredients, a combination of:
 (i) a first active ingredient that induces a high level of extracellular GABA or increases GABA transmission; and   (ii) a second active ingredient selected from the group consisting of taurine, a taurine precursor, a taurine metabolite, a taurine derivative, a taurine analog and a substance required for the taurine biosynthesis,   and one or more pharmaceutically acceptable excipients.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the first active ingredient that induces a high level of extracellular GABA consists of 4-amino-5-hexenoic acid, its racemic mixture or the active isomer. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the second active ingredient consists of taurine. 
     
     
         4 . A method of preventing or inhibiting the undesirable side-effects caused to a human or an animal organism by an active ingredient that induces a high level of extracellular GABA or increases GABA transmission, comprising administering to a subject in need thereof an effective amount of a substance selected from the group consisting of taurine, a taurine precursor, a taurine metabolite, a taurine derivative, a taurine analog and a substance required for taurine biosynthesis. 
     
     
         5 . The method according to  claim 4 , wherein the taurine precursor is selected from the group consisting of cysteine, cystathionine, homocysteine, S-adenosylhomocysteine, serine, N-acetyl-cysteine, glutathione, N-formylmethionine, S-adenosylmethionine, betaine and methionine. 
     
     
         6 . The method according to  claim 4 , wherein the taurine metabolite is selected from the group consisting of hypotaurine, thiotaurine, and taurocholate. 
     
     
         7 . The method according to  claim 4 , wherein the taurine derivative is selected from the group consisting of of acetylhomotaurinate, and piperidino-, benzamido-, phthalimido- or phenylsuccinylimido taurine derivatives, taurolidine, taurultam and taurinamide, chlorohydrate-N-isopropylamide-2-(1-phenylethyl)aminoethanesulfonic acid. 
     
     
         8 . The method according to  claim 4 , wherein the taurine analog is selected from the group consisting of (+/−) piperidine-3-sulfonic acid (PSA), 2-aminoethylphosphonic acid (AEP), (+/−)2-acetylaminocyclohexane sulfonic acid (ATAHS), 2-aminobenzenesulfonate (ANSA), hypotaurine, (+/−)trans-2-aminocyclopentanesulfonic acid (TAPS) 8-tétrahydroquinoleine sulfonic acid (THQS), N-2-hydroxyethylpiperazine-N′-2-ethane sulphonic acid (HEPES), beta-alanine, glycine, guanidinoethylsulfate (GES), 3-acetamido-1-propanesulfonic acid (acamprosate). 
     
     
         9 . The method according to  claim 4 , wherein the substance required for the taurine biosynthesis is selected from the group consisting of vitamin B6, vitamin B12, folic acid, riboflavin, pyridoxine, niacin, thiamine, and pantothenic acid. 
     
     
         10 . The method according to  claim 4 , wherein the active ingredient that induces a high level of extracellular GABA or increases GABA receptor activation is selected from the group consisting of a GABA-aminotransferase inhibitor, a GABA transporter blocker, a glutamate decarboxylase activator and a GABA receptor agonist or modulator. 
     
     
         11 . The method according to  claim 10 , wherein the GABA-aminotransferase inhibitor consists of 4-amino-5-hexenoic acid (vigabatrin), its racemic mixture or the active isomer, valproate, (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid, (1R,4S)-4-amino-2-cyclopentene-1-carboxylic acid, (1S,4R)-4-amino-2-cyclopentene-1-carboxylic acid, (4R)-4-amino-1-cyclopentene-1-carboxylic acid, (4S)-4-amino-1-cyclopentene-1-carboxylic acid, (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid, 1H-tetrazole-5-(alpha-vinyl-propanamine), 2,4-diaminobutanoate, 2-oxoadipic acid, 2-oxoglutarate, 2-thiouracil, 3-chloro-4-aminobutanoate, 3-mercaptopropionic acid, 3-methyl-2-benzothiazolone hydrazone hydrochloride, 3-phenyl-4-aminobutanoate, 4-ethynyl-4-aminobutanoate, 5-diazouracil, 5-fluorouracil, aminooxyacetate, beta-alanine, cycloserine and D-cycloserine. 
     
     
         12 . The method according to  claim 10 , wherein the GABA transporter blocker consists of tiagabine. 
     
     
         13 . The method according to  claim 10 , wherein the GABA receptors agonists or modulators are selected from the group consisting of, topiramate, felbamate, tramadol, oxcarbazepine, carbamazepine, eszopiclone, zopiclone, baclofen, gammaHydroxybutyric acid, imidazopyridines like zaleplon, zolpidem, zopiclone phenytoin, propofol, phenytoin, benzodiazepines and barbiturates.