Abstract

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 anti-convulsant 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 resposible for antagonism of bicuculline-induced convulsions.

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