Correlation of [14C]muscimol concentration in rat brain with anticonvulsant activity.
Muscimol, an in vivo and in vitro GABA agonist, has anticonvulsant activity against bicuculline-induced seizures when given systemically to rats. To determine whether parent compound or a metabolite possessed the anticonvulsant activity, experiments were performed with [14C]muscimol. Anticonvulsant activity was determined by the percent of animals protected against tonic forelimb extension induced by bicuculline. Brain and urine were analyzed for unchanged [14C]muscimol by thin-layer chromatography. The time course of anticonvulsant activity and [14C]muscimol concentration in brain after intravenous injection were similar. Peak brain concentration of [14C]muscimol and maximal protection against bicuculline-induced seizures occurred simultaneously. These data suggest that intravenously administered [14C]muscimol rapidly penetrates brain tissue and parent compound is responsible for antagonism of bicuculline-induced convulsions.
D000818:Animals; D000927:Anticonvulsants; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats
D000927:Anticonvulsants; D010080:Oxazoles; D009118:Muscimol; D001640:Bicuculline