FELBAMATE ANTAGONIZES ISONIAZID-INDUCED AND FG-7142-INDUCED REDUCTIONOF GABA(A) RECEPTOR FUNCTION IN MOUSE-BRAIN

Injection of the antiepileptic drug, felbamate (2-phenyl-1,3-propanedi ol dicarbamate), into mice reduced in a dose-dependent manner (150-300 mg/kg i.p.) the isoniazid (200 mg/kg s.c.)-induced increase in ex viv o binding of t-[S-35]butylbicyclo-phosphorothionate ([S-35]TBPS) to ce rebral cortical and hippocampal membranes. The same doses of felbamate reduced significantly the number of mice exhibiting isoniazid-induced seizures. A dose of felbamate (50 mg/kg) ineffective in isoniazid-tre ated mice completely antagonized the increase of [S-35]TBPS binding el icited by FG 7142 (N-methyl-beta-carboline-3-carboxamide), a benzodiaz epine receptor inverse agonist. The above effects of felbamate resembl ed those of diazepam. Accordingly, the combination of ineffective dose s of felbamate (50 mg/kg) and diazepam (0.2 mg/kg) elicited a marked d ecrease of [S-35]TBPS binding. The results indicate that facilitation of gamma-aminobutyric acid type A (GABA(A)) receptor function may play a role in the anticonvulsant action of felbamate.