Effects of anticonvulsant drugs on the cerebral enzymes metabolizing GABA.

The effect of anticonvulsant drugs on the activity of enzymes responsible for the further metabolism of GABA has been studied in mouse brain homogenates. Slight inhibition (5 to 20%) of 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 to 20% at low concentrations (0.01 to 0.1 mM) of diazepam, carbamazepine, beclamide, acetazolamide, and di-n-propylacetate, and by 40% or more at high concentrations (2.5 to 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.