Felbamate antagonizes isoniazid- and FG 7142-induced reduction of GABAA receptor function in mouse brain.
Injection of the antiepileptic drug, felbamate (2-phenyl-1,3-propanediol 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 vivo binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to cerebral 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-treated mice completely antagonized the increase of [35S]TBPS binding elicited by FG 7142 (N-methyl-beta-carboline-3-carboxamide), a benzodiazepine receptor inverse agonist. The above effects of felbamate resembled those of diazepam. Accordingly, the combination of ineffective doses of felbamate (50 mg/kg) and diazepam (0.2 mg/kg) elicited a marked decrease of [35S]TBPS binding. The results indicate that facilitation of gamma-aminobutyric acid type A (GABAA) receptor function may play a role in the anticonvulsant action of felbamate.
Serra
M
M
Department of Experimental Biology, B. Loddo, University of Cagliari, Italy.
Ghiani
C A
CA
Spano
S
S
Biggio
G
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001681:Biological Assay / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000502:physiology; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002243:Carbolines / Q000037:antagonists & inhibitors*; D000078328:Felbamate; D007538:Isoniazid / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D018079:Receptors, GABA / Q000187:drug effects* / Q000502:physiology
D000927:Anticonvulsants; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002243:Carbolines; D048448:Phenylcarbamates; D011409:Propylene Glycols; D018079:Receptors, GABA; C035874:FG 7142; C037476:tert-butylbicyclophosphorothionate; D007538:Isoniazid; D000078328:Felbamate