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.