title: Effects of anticonvulsant drugs on the cerebral enzymes metabolizing GABA.
abstract: 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.
authors.affiliation: Department of Neurology, Institute of Psychiatry, De Crespigny Park, London,l England.
authors.forename: M C
authors.initials: MC
authors.lastname: Sawaya
authors.forename: R W
authors.initials: RW
authors.lastname: Horton
authors.forename: B S
authors.initials: BS
authors.lastname: Meldrum
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D008297:Male; D051379:Mice; D050644:Succinate-Semialdehyde Dehydrogenase; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D000445:Aldehyde Oxidoreductases; D050644:Succinate-Semialdehyde Dehydrogenase; D000612:4-Aminobutyrate Transaminase