Effect of convulsant and anticonvulsant agents on level and metabolism of gamma-aminobutyric acid in mouse brain.
1. The effect of the convulsant agents pentetrazole, picrotoxin, bicuculline, strychnine and isoniazid on the central level of gamma-aminobutyric acid (GABA) and the activity of the enzymes glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) from mice brain was studied in vivo and vitro. In vivo, convulsant doses of picrotoxin and isoniazid lowered the level of GABA and the activity of GAD, whereas strychnine and bicuculline had no such effect. Pentetrazole inhibited GAD, but did not alter the GABA content. In vitro, all convulsants, except bicuculline, inhibited the activity of GAD; however, the concentrations of strychnine were far beyond the range that is reached in vivo by convulsant doses. Only isoniazid inhibited the activity of GABA-T in vivo as well as in vitro. 2. Phenobarbital, ethosuximide and trimethadione were about equally active in preventing convulsions induced by strychnine and picrotoxin, whereas diazepam was 9 times, and sodium valproate 3.5 times more active against convulsions elicited by picrotoxin. Phenytoin up to 100 mg/kg was ineffective against all chemoconvulsants. 3. Diazepam, sodium valproate, ethosuximide and trimethadione antagonized the inhibition of GAD and the decrease in GABA concentrations caused by isoniazid. Phenobarbital and phenytoin prevented the decrease of GABA but did not reverse the inhibition of GAD. 4. The results suggest a role played by the transmitter pool of GABA in the convulsant action of chemoconvulsants and in the anticonvulsant effect of antiepileptics clinically used in petit mal epilepsy.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007538:Isoniazid / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D000927:Anticonvulsants; D003292:Convulsants; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D007538:Isoniazid