Effects of Anticonvulsant Drugs on the Cerebral Enzymes Metabolizing GABA

Abstract

Studies were done on mouse brain homogenates. Slight inhibition (5-20%) of .gamma.-aminolbutyric acid transaminase [GABA-T] activity was seen with chlordiazepoxide (0.1 mM), ethosuximide (0.1 mM) and di-n-propylacetate (0.1 mM). No anticonvulsant drug (even at a concentration of 10 mM) produced inhibition comparable to that seen with amino-oxyacetic acid (65% at 0.01 mM). Succinic semialdehyde dehydrogenase activity was inhibited by 10-20% at low concentrations (0.01-0.1 mM) of diazepam, carbamazepine, beclamide, acetazolamide and di-n-propylacetate, and by 40% or more at high concentrations (2.5-10.0 mM) of diazepam, phenobarbital, carbamazepine, beclamide, and di-n-propylacetate. Interference with the further metabolism of GABA may contribute to the antiepileptic action of drugs or to the acute neurological toxicity of anticonvulsant agents.