Comparison of anticonvulsant effect of pentobarbital and phenobarbital against seizures induced by maximal electroschock and picrotoxin in rats

Abstract

Pentobarbital and phenobarbital exhibited anticonvulsant effect against maximal electroshock (MES) and picrotoxin-induced seizures in rats. Bicuculline, a GABA A receptor antagonist, reversed the anticonvulsant effect of pentobarbital, but not of phenobarbital, at a dose having no effect per se. Although picrotoxin (2 mg/kg, IP) potentiated MES seizures, it did not reverse the anticonvulsant effect due to either pentobarbital or phenobarbital. GABA B receptor antagonists such as γ-amino-n-valeric acid and homotaurine failed to modify the anticonvulsant effect due to pentobarbital or phenobarbital. Furthermore, GABA A agonist muscimol but not baclofen, a GABA B receptor agonist, exhibited the anticonvulsant effect against MES-induced seizures. However, baclofen when combined with sub-effective dose of pentobartibal or phenobarbital offered protection against MES seizures. Pentobarbital and phenobarbital were effective in almost equivalent doses against MES, as well as against picrotoxin-induced seizures. These observations indicated that pentobarbital exhibits anticonvulsant effect against MES seizures through the involvement of GABA A receptors, and activation of GABA B receptors alone does not seem to play any significant role in MES seizures and in the anticonvulsant effect of pentobarbital. However, activation of GABA B receptor does potentiate the facilitatory effect of barbiturates on GABA Aergic transmission and in their anti-MES effect. Moreover, these results also suggest that the anticonvulsant effect of barbiturates against MES-seizures may involve other mechanisms in addition to GABA Aergic transmission.