2.6.1.19 (+/-)-(1S,2R,4S,5S)-4-amino-6,6-difluorobicyclo[3.1.0]hexane-2-carboxylic acid 10 mM, weak, reversible inhibitor 135494 2.6.1.19 (+/-)-(1S,2S,4S,5S)-4-amino-6,6-difluorobicyclo[3.1.0]hexane-2-carboxylic acid 10 mM, weak, reversible inhibitor 135495 2.6.1.19 (+/-)piperidine-3-sulfonic acid - 62544 2.6.1.19 (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid mechanism-based inactivation, adduct formed is derived from enamine mechanism 124887 2.6.1.19 (1R,4S)-4-amino-2-cyclopentene-1-carboxylic acid analogue of 4-aminobutanoate, vigabatrin 33020 2.6.1.19 (1R,4S)-4-amino-3-fluorocyclopent-2-enecarboxylic acid weak reversible inhibition in the presence of beta-mercaptoethanol 62539 2.6.1.19 (1R,4S)-4-amino-3-pentafluoroethylcyclopent-2-enecarboxylic acid weak reversible inhibition in the presence of beta-mercaptoethanol 62540 2.6.1.19 (1R,4S)-4-amino-3-trifluoromethylcyclopent-2-enecarboxylic acid irreversible inhibition in the presence of beta-mercaptoethanol 135490 2.6.1.19 (1S,2S,3E)-2-amino-3-(fluoromethylidene)cyclopentanecarboxylic acid monofluorinated analog of inhibitor CPP-115. Compound produces a metabolite that induces disruption of the Glu270-Arg445 salt bridge of GABA transaminase to accommodate interaction between the metabolite formyl group and Arg445. The inactivation mechanism is initiated by Schiff base formation with the active site pyridoxal 5'-phosphate, followed by gamma-proton removal 209148 2.6.1.19 (1S,2S,3Z)-2-amino-3-(fluoromethylidene)cyclopentanecarboxylic acid monofluorinated analog of inhibitor CPP-115. Compound produces a metabolite that induces disruption of the Glu270-Arg445 salt bridge of GABA transaminase to accommodate interaction between the metabolite formyl group and Arg445. The inactivation mechanism is initiated by Schiff base formation with the active site pyridoxal 5'-phosphate, followed by gamma-proton removal 209149 2.6.1.19 (1S,3S)-(Z)-3-amino-4-(2,2,2-trifluoroethylidene)cyclopentanecarboxylic acid inhibition in the presence of beta-mercaptoethanol 135491 2.6.1.19 (1S,3S)-3-amino-4-(2,2,2-trifluoro-1-trifluoromethylethylidene)-cyclopentanecarboxylic acid weak reversible inhibition in the presence of beta-mercaptoethanol 62541 2.6.1.19 (1S,3S)-3-amino-4-difluoromethylenecyclopentanecarboxylic acid potent irreversible inhibitor 62548 2.6.1.19 (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid i.e. CPP-115, high inhibition of GABA-AT. Potential mechanism of inactivation of GABA-AT by CPP-115, overview. CPP-115 has been designed to inactivate GABA-AT via a Michael addition mechanism that would lead to a covalent adduct with the enzyme, similar to that with vigabatrin. But it is discovered from the crystal structure of GABAT inactivated by CPP-115 that the enzyme forms a noncovalent, tightly bound complex with CPP-115 via strong electrostatic interactions between the two carboxylate groups in the resulting metabolite with Arg192 and Arg445 in the active site. Inactivation is initiated by Schiff base formation between CPP-115 and the lysine-bound PLP, followed by gamma-proton removal and tautomerization, resulting in a highly reactive Michael acceptor. Before Lys329 can attack this Michael acceptor, catalytic hydrolysis of the difluoromethylenyl group occurs, leading to the PLP-bound dicarboxylate metabolite, which elicits a conformational change in the enzyme and tightly binds to Arg192 and Arg445 via electrostatic interactions. Molecular dynamic simulations and computer modeling indicate a movement of the difluoromethylenyl group of the Michael acceptor away from Lys329 upon enzyme-catalyzed tautomerization, leaving it too far away from Lys329 for nucleophilic attack. The enzyme catalyzes its hydrolysis instead 251542 2.6.1.19 (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid i.e. CPP-115, high inhibition of GABA-AT. Potential mechanism of inactivation of GABA-AT by CPP-115, overview. CPP-115 has been designed to inactivate GABA-AT via a Michael addition mechanism that would lead to a covalent adduct with the enzyme, similar to that with vigabatrin. But it is discovered from the crystal structure of GABAAT inactivated by CPP-115 that the enzyme forms a noncovalent, tightly bound complex with CPP-115 via strong electrostatic interactions between the two carboxylate groups in the resulting metabolite with Arg192 and Arg445 in the active site. Inactivation is initiated by Schiff base formation between CPP-115 and the lysine-bound PLP, followed by gamma-proton removal and tautomerization, resulting in a highly reactive Michael acceptor. Before Lys329 can attack this Michael acceptor, catalytic hydrolysis of the difluoromethylenyl group occurs, leading to the PLP-bound dicarboxylate metabolite, which elicits a conformational change in the enzyme and tightly binds to Arg192 and Arg445 via electrostatic interactions. Molecular dynamic simulations and computer modeling indicate a movement of the difluoromethylenyl group of the Michael acceptor away from Lys329 upon enzyme-catalyzed tautomerization, leaving it too far away from Lys329 for nucleophilic attack. The enzyme catalyzes its hydrolysis instead 251542 2.6.1.19 (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid - 251542 2.6.1.19 (1S,4R)-4-amino-2-cyclopentene-1-carboxylic acid analogue of 4-aminobutanoate, vigabatrin 51159 2.6.1.19 (1S,4S)-2-(difluoromethylidene)-4-(1H-tetrazol-5-yl)cyclopentanamine time-dependent inactivation, ratio kinact/KI value at pH 8.0 is 2.48 per min and mM 68340 2.6.1.19 (2E)-4-methylpentan-2-one N-(2,4-dimethylphenyl)semicarbazone 57% inhibition at 0.125 mM 135048 2.6.1.19 (2E)-butan-2-one N-(2,4-dimethylphenyl)semicarbazone 89% inhibition at 0.0625 mM 135047 2.6.1.19 (4R)-4-amino-1-cyclopentene-1-carboxylic acid analogue of 4-aminobutanoate, vigabatrin 16891 2.6.1.19 (4S)-4-amino-1-cyclopentene-1-carboxylic acid analogue of 4-aminobutanoate, vigabatrin 51187 2.6.1.19 (R,S)-4-amino-3-fluorobutanoic acid the (R)-enantiomer inhibits the transamination of gamma-aminobutanoic acid 10 times more effectively than the (S)-enantiomer. On binding of free 4-amino-3-fluorobutanoic acid to enzyme the optimal conformation places the C-NH3 + and C-F bonds gauche in the (R)-enantiomer but anti in the (S)-enantiomer 37808 2.6.1.19 (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid a highly potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of addiction, design, synthesis method and mechanism, overview. Enzyme-bound structure analysis shows binding between the enzyme and a stable PLP-inhibitor noncovalent complex, rather than covalent modification, tautomeric forms of the structure of inhibitor-inactivated GABA-AT (eight theoretical tautomers of inhibitor-inactivated GABA-AT) 251681 2.6.1.19 (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid i.e. OV329, synthesis method, overview 251681 2.6.1.19 (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid mechanism-based inactivator, reacts via aromatization mechanism 51201 2.6.1.19 (Z)-4-amino-2-butenoic acid - 155458 2.6.1.19 1-(4-acetylphenyl)-3-(4-bromophenyloxy)-pyrrolidine-2,5-dione - 209129 2.6.1.19 1-(4-acetylphenyl)-3-(salicyldehydroxy)-pyrrolidine-2,5-dione - 209130 2.6.1.19 1H-tetrazole-5-(alpha-vinyl-propanamine) - 56733 2.6.1.19 2,4-diaminobutanoate kinetics 12296 2.6.1.19 2,4-diaminobutanoate not 12296 2.6.1.19 2,4-dimethylphenyl semicarbazide hydrochloride 90% inhibition at 0.0625 mM 135489 2.6.1.19 2-Aminobenzenesulfonate - 9007 2.6.1.19 2-aminobutanoate - 1743 2.6.1.19 2-aminoethane phosphonic acid - 62543 2.6.1.19 2-N-(acetylamino)cyclohexane sulfonic acid - 62542 2.6.1.19 2-oxoadipic acid - 12317 2.6.1.19 2-oxoglutarate - 34 2.6.1.19 2-oxoglutarate substrate inhibition 34 2.6.1.19 2-Thiouracil weak 4203 2.6.1.19 3-(aminomethyl)benzoic acid poor competitive inhibitor 69091 2.6.1.19 3-aminocyclohexanecarboxylic acid 10 mM 135496 2.6.1.19 3-chloro-1-(4-hydroxyphenyl)propan-1-one irreversible and potent inhibitor, about 30% residual activity at 0.06 mM, 2-oxoglutarate prevents the enzyme from inactivation 77420 2.6.1.19 3-Chloro-4-aminobutanoate - 91391 2.6.1.19 3-Mercaptopropionic acid - 3437 2.6.1.19 3-Methyl-2-benzothiazolone hydrazone hydrochloride - 12349 2.6.1.19 3-Phenyl-4-aminobutanoate - 91538 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-(4-ethylphenyl)butanamide - 252090 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-(4-fluorophenyl)butanamide - 252091 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-(4-iodophenyl)butanamide - 252092 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-(4-methoxyphenyl)butanamide - 252093 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-(4-nitrophenyl)butanamide - 252094 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-p-tolylbutanamide - 252095 2.6.1.19 4-(1,3-dioxoisoindolin-2-yl)-N-phenylbutanamide - 252096 2.6.1.19 4-(aminomethyl)-1H-pyrrole-2-carboxylic acid - 19710 2.6.1.19 4-(aminomethyl)furan-2-carboxylic acid - 19708 2.6.1.19 4-(aminomethyl)furan-3-carboxylic acid - 19711 2.6.1.19 4-(aminomethyl)thiophene-2-carboxylic acid - 19709 2.6.1.19 4-(aminomethyl)thiophene-3-carboxylic acid - 28832 2.6.1.19 4-acryloylphenol potent inhibitor 62546 2.6.1.19 4-amino-2-fluorobutanoate reversible, competitive to 4-aminobutanoate 51384 2.6.1.19 4-amino-5-fluoropentanoic acid potent irreversible inhibitor 135493 2.6.1.19 4-Amino-hex-5-enoic acid substrate analogue, irreversible, in vitro and in vivo 91636 2.6.1.19 4-aminohex-5-enoic acid - 23509 2.6.1.19 4-aminohex-5-enoic acid i.e. gamma-vinyl GABA, competitive, does not affect transamination process of 2-oxoglutarate 23509 2.6.1.19 4-Aminohex-5-ynoic acid irreversible, in vitro and in vivo, kinetics 20000 2.6.1.19 4-ethynyl-4-aminobutanoate - 127335 2.6.1.19 4-hydroxybenzaldehyde potent inhibitor 711 2.6.1.19 4-hydroxybenzaldehyde IC50: 0.0165 mM, competitive inhibition 711 2.6.1.19 4-hydroxybenzaldehyde competitive inhibitor of GABA transaminase 711 2.6.1.19 4-hydroxybenzylamine IC50: 0.0154 mM, competitive inhibition 62547 2.6.1.19 5,5'-dithiobis-2-nitrobenzoic acid 95% loss of activity 5368 2.6.1.19 5-(aminomethyl)-1H-pyrrole-2-carboxylic acid - 19707 2.6.1.19 5-(aminomethyl)furan-2-carboxylic acid - 19705 2.6.1.19 5-(aminomethyl)thiophene-2-carboxylic acid - 19706 2.6.1.19 5-amino-1,3-cyclohexadienylcarboxylate - 88727 2.6.1.19 5-Diazouracil weak 10541 2.6.1.19 5-fluorouracil weak 812 2.6.1.19 5-fluorouracil - 812 2.6.1.19 5-Iodouracil 84% inhibition at 1 mM 3608 2.6.1.19 5-Nitrouracil weak 4494 2.6.1.19 5-Thiouracil weak 29611 2.6.1.19 6-Azathymine - 10550 2.6.1.19 6-Azauracil 63% inhibition at 1 mM, reversible by dialysis, not by pyridoxal phosphate addition 5506 2.6.1.19 acetic acid - 751 2.6.1.19 adipic acid - 3323 2.6.1.19 ADP reversible 13 2.6.1.19 alpha-alanine - 30646 2.6.1.19 Aminooxyacetate - 1374 2.6.1.19 Aminooxyacetate kinetics 1374 2.6.1.19 Aminooxyacetate 99% inhibition at 1 mM 1374 2.6.1.19 Aminooxyacetate 80% inhibition at 2 mM 1374 2.6.1.19 ATP reversible 4 2.6.1.19 Ba2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 111 2.6.1.19 Baclofen injection of 0.01 mg/g body weight reduces GABA-T mRNA level 2fold; i.p. injection of sexually regressed female goldfish results in significant increase in serum luteinising hormone after 6 h. About 2fold decrease both in glutamic acid decarboxylase 67 and gamma-aminobutanoate transaminase mRNa in the hypothalamus 20134 2.6.1.19 beta-Alanine not 494 2.6.1.19 beta-Alanine - 494 2.6.1.19 beta-Alanine competitive inhibitor of pyruvate-dependent GABA-T activity 494 2.6.1.19 beta-Alanine moderate inhibitor; moderate inhibitor 494 2.6.1.19 beta-cypermethrin GABA transaminase activity detected is significantly decreased in the cerebral cortex of mice 2 h after beta-cypermethrin administration. beta-Cypermethrin (80 mg/kg) significantly increases GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. The number of positive granules is increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg beta-cypermethrin. No significant changes are found in glutamate decarboxylase activity, or the expression of GABA transaminase protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg beta-cypermethrin causes a significant decrease in GABAA receptors mRNA expression 4 h after administration 166769 2.6.1.19 Branched-chain fatty acids - 46457 2.6.1.19 Butyric acid - 1556 2.6.1.19 Ca2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 15 2.6.1.19 carbonyl reagents - 9395 2.6.1.19 Cd2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 52 2.6.1.19 cis-3-aminocyclohex-4-ene-1-carboxylic acid conformationally rigid analogue of vigabatrin, mechanism 113205 2.6.1.19 Co2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 23 2.6.1.19 Cu2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 19 2.6.1.19 Cu2+ - 19 2.6.1.19 cycloserine 90% inhibition at 1 mM 2837 2.6.1.19 D-cycloserine - 874 2.6.1.19 D-penicillamine - 2733 2.6.1.19 dioxan 5% v/v 93221 2.6.1.19 Divalent metal ions with decreasing efficiency: Hg2+, Cd2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 16222 2.6.1.19 DL-3-amino-1-cyclopentene-1-carboxylic acid analogue of 4-aminobutanoate, vigabatrin 22106 2.6.1.19 DL-cysteine - 12515 2.6.1.19 DL-trans-4-amino-2-cyclopentene-1-carboxylic acid analogue of 4-aminobutanoate, vigabatrin 51637 2.6.1.19 ethanol 10% v/v, weak 69 2.6.1.19 ethanol in presence of disulfiram, i.e. N,N,N’,N’-tetraethylthiuram disulfide 69 2.6.1.19 ethanolamine O-sulfate active-site directed, ir, in vitro and in vivo, kinetics 51645 2.6.1.19 ethylamine-2-sulfonic acid i.e. taurine, competitive 57673 2.6.1.19 falcarindiol active-site directed, irreversible, 23% residual activity at 14 mM, isolate of root of Angelica dahurica 56732 2.6.1.19 gabaculine 98% inhibition at 1 mM 1869 2.6.1.19 gabaculine - 1869 2.6.1.19 gabaculine i.e. 5-amino-1,3-cyclohexadienylcarboxylate, ir, kinetics; not its tert-butylcarbamate derivative 1869 2.6.1.19 gabaculine 80% inhibition at 2 mM 1869 2.6.1.19 gabaculine IC50: 0.0018 mM, potent and irreversible inhibitor 1869 2.6.1.19 gabaculine highly specific GABAtransaminase inhibitor 1869 2.6.1.19 gamma-vinyl 4-aminobutanoate 0.1 mM, complete inhibition 135492 2.6.1.19 gastrodigenin 30.87% inhibition at 0.01 mM 135498 2.6.1.19 GDP reversible 53 2.6.1.19 glutamic acid - 3205 2.6.1.19 Glutarate - 545 2.6.1.19 glycine competitive inhibitor of pyruvate-dependent GABA-T activity 72 2.6.1.19 glyoxylate weak 101 2.6.1.19 HgCl2 strong, 50% inhibition at 0.007 mM 110 2.6.1.19 HgCl2 - 110 2.6.1.19 HgCl2 24% inhibition at 0.05 mM, pyridoxal 5'-phosphate protects 110 2.6.1.19 hydrazine - 684 2.6.1.19 hydroxylamine - 85 2.6.1.19 imperatorin active-site directed, irreversible, 14% residual activity at 14 mM, isolate of root of Angelica dahurica 11559 2.6.1.19 KCN - 161 2.6.1.19 Lysyl reagents 2-oxoglutarate protects 99403 2.6.1.19 Maleate - 575 2.6.1.19 methanol 10% v/v, weak 83 2.6.1.19 Mg2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 6 2.6.1.19 Mn2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 11 2.6.1.19 monoiodoacetate not 1473 2.6.1.19 monoiodoacetate - 1473 2.6.1.19 additional information no inhibition by 6-azauridine, 6-azauridine 5'-phosphate, uracil, (iso)orotic acid, cytosine, thymine, dihydrothymine, 2-thiocytosine, thiourea; not inhibitory: 5-aminouracil 2 2.6.1.19 additional information - 2 2.6.1.19 additional information no inhibition by 3-aminopropane-1-sulfonic acid, isoguvacine (i.e. 1,2,3,4-tetrahydro-1-methyl-3-pyridine carboxylic acid), baclofen (i.e. beta-(aminomethyl)-4-chlorobenzenepropanoic acid), bicuculline, picrotoxin, Schistocerca gregaria: antiserum against sheep enzyme 2 2.6.1.19 additional information no inhibition by chelating agents, non-substrate L- or D-amino acids, metal ions 2 2.6.1.19 additional information no substrate inhibition: 4-aminobutanoate 2 2.6.1.19 additional information (+/-)-(1S,3S,4S)-3-amino-4-fluorocyclohexanecarboxylic acid and (cis)-3-amino-5,5-difluorocylcohexanecarboxylic acid are no an inhibitors of GABA-AT at a concentration of 10 mM 2 2.6.1.19 additional information the methanol extract from Melissa officinalis is a potent in vitro inhibitor of GABA-T with IC50 of 0.55 mg/ml, inhibition decreases in the order: methanol extract, water extract, ethyl acetate extract and hexane extract (not inhibitory) 2 2.6.1.19 additional information a series of gamma-aminobutyric acid (GABA) derivatives obtained from 4-(1,3-dioxoisoindolin-2-yl)butanoic acid are synthesized and analyzed as inhibitory ligands docking against human ABAT as well as pig ABAT receptors. Active site docking study, overview 2 2.6.1.19 additional information molecular dynamics simulations, design of mechanism-based inhibitors, drug design, overview 2 2.6.1.19 Muscimol i.e. 5-(aminomethyl)-3-isoxazolol 20386 2.6.1.19 Muscimol injection of 0.001 mg/g body weight reduces GABA-T mRNA level 15fold; i.p. injection of sexually regressed female goldfish results in significant increase in serum luteinising hormone after 6 h. About 10fold decrease in glutamic acid decarboxylase 65 and 15fold in gamma-aminobutanoate transaminase mRNa in the hypothalamus 20386 2.6.1.19 N-(2,4-dichlorophenyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide - 252455 2.6.1.19 N-(2,4-difluorophenyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide - 252457 2.6.1.19 N-(4-bromophenyl)-3-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydroindeno[1,2-c]pyrazole-2(3H)-carboxamide molecular docking to propose the binding interaction with a three-dimensional structural model of the gamma-aminobutyric acid amino transferase. The compound successfully binds to the active pocket of the enzyme with good predicted affinities 209141 2.6.1.19 N-(4-bromophenyl)-3-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydroindeno[1,2-c]pyrazole-2(3H)-carboxamide molecular docking to propose the binding interaction with a three-dimensional structural model of the gamma-aminobutyric acid amino transferase. The compound successfully binds to the active pocket of the enzyme with good predicted affinities 209142 2.6.1.19 N-(4-bromophenyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide - 252513 2.6.1.19 N-(4-chloro-2-iodophenyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide - 252516 2.6.1.19 N-(4-chloro-2-methylphenyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide - 252517 2.6.1.19 N-(4-chlorophenyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide - 252518 2.6.1.19 Ni2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 38 2.6.1.19 oleanolic acid 20.2% inhibition at 0.1 mg/ml 2975 2.6.1.19 ornithine competitive inhibitor of pyruvate-dependent GABA-T activity 576 2.6.1.19 ornithine moderate inhibitor; moderate inhibitor 576 2.6.1.19 oxalacetate - 2575 2.6.1.19 p-chloromercuribenzoate strong 43 2.6.1.19 p-chloromercuribenzoate - 43 2.6.1.19 phenylhydrazine - 398 2.6.1.19 pimelic acid - 15923 2.6.1.19 propan-2-one N-(2,4-dimethylphenyl)semicarbazone 44% inhibition at 0.25 mM 135046 2.6.1.19 propionic acid - 1724 2.6.1.19 pyruvate - 31 2.6.1.19 rosmarinic acid 40.2% inhibition at 0.1 mg/ml 2035 2.6.1.19 S-vigabatrin ratio kinact/KI is1.7 per min and mM at pH 8.5, 0.11per min and mM at pH 6.5, respectively 143936 2.6.1.19 SH-group reagents 2-oxoglutarate protects 20951 2.6.1.19 SH-group reagents - 20951 2.6.1.19 SH-group reagents 2-mercaptoethanol or DTT reactivates 20951 2.6.1.19 Sr2+ order of decreasing inhibitory potency: Hg2+, Cd2+, Cu2+, Co2+, Ba2+, Sr2+, Ni2+, Mn2+, Ca2+, Mg2+ 338 2.6.1.19 succinate - 58 2.6.1.19 Succinic semialdehyde substrate inhibition 809 2.6.1.19 Succinic semialdehyde - 809 2.6.1.19 tetrazole-5-(alpha-vinyl-propanamine) - 62545 2.6.1.19 trimethylcitryl-beta-D-galactopyranoside 56.8% inhibition at 0.01 mM 135497 2.6.1.19 ursolic acid 19.9% inhibition at 0.1 mg/ml 2291 2.6.1.19 Valproic acid 65.4% inhibition at 0.01 mM 2424 2.6.1.19 vigabatrin gamma-vinyl GABA, anticonvulsant, induces spontaneous release of 4-aminobutanoate 3140 2.6.1.19 vigabatrin mechanism 3140 2.6.1.19 vigabatrin - 3140 2.6.1.19 vigabatrin IC50: 0.35 mM 3140 2.6.1.19 vigabatrin triggers a massive synaptic plasticity in retinal areas showing a normal layering of the retina shown by the withdrawal of rod but not cone photoreceptor terminals from the outer plexiform layers towards their cell bodies. Both rod bipolar cells and horizontal cells exhibit dendritic sprouting into the photoreceptor nuclear layer. Withdrawing rod photoreceptors appear to form ectopic contacts with growing postsynaptic dendrites. Neuronal plasticity is highly suggestive of an impaired glutamate release by photoreceptors 3140 2.6.1.19 vigabatrin chronical administration via drinking water at 30 and 81 mg per kg and day. Vigabatrin completely and reversibly eliminates the psychophysical evidence of tinnitus at both doses 3140 2.6.1.19 vigabatrin competitive inhibitor of pyruvate-dependent GABA-T activity 3140 2.6.1.19 vigabatrin complete inhibition at 0.5 mM 3140 2.6.1.19 vigabatrin FDA-approved drug, inactivator of GABA-AT, moderate activity 3140 2.6.1.19 [2-(aminomethyl)phenyl]acetic acid poor competitive inhibitor 69093 2.6.1.19 [3-(aminomethyl)phenyl]acetic acid poor competitive inhibitor 69092