Comparative study of the inhibition of GABA aminotransferase by different anticonvulsant drugs.
Fourteen anticonvulsant drugs were examined for their effects on the activity of GABA-alpha-oxoglutarate aminotransferase (GABA-T). Only the nonspecific enzyme inhibitor aminooxyacetic acid (IC50 2.7 microM) proved to be as potent as the catalytic inhibitors gabaculine (1.8 microM), gamma-acetylenic GABA (150 microM) and gamma-vinyl GABA (350 microM) with respect to inhibition of GABA-T. 2-Methyl-2-ethyl caproic acid, ethanolamine O-sulphate and isoniazid were less effective inhibitors of the GABA-T activity (IC50 greater than 1 mM). None of the clinically established antiepileptic drugs tested (viz. phenobarbital, phenytoin, diazepam, valproate, trimethadione, dimethadione and ethosuximide) produced inhibition comparable to the aforementioned drugs. A slight inhibition of GABA-T (8 to 28%) was seen only with high concentrations of trimethadione, valproate and ethosuximide.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D007700:Kinetics; D008297:Male; D051379:Mice; D000637:Transaminases / Q000037:antagonists & inhibitors*
D000927:Anticonvulsants; D000637:Transaminases; D000612:4-Aminobutyrate Transaminase