Comparison of anticonvulsant effect of pentobarbital and phenobarbital against seizures induced by maximal electroshock and picrotoxin in rats.
Pentobarbital and phenobarbital exhibited anticonvulsant effect against maximal electroshock (MES) and picrotoxin-induced seizures in rats. Bicuculline, a GABAA 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. GABAB receptor antagonists such as delta-amino-n-valeric acid and homotaurine failed to modify the anticonvulsant effect due to pentobarbital or phenobarbital. Furthermore, GABAA agonist muscimol but not baclofen, a GABAB receptor agonist, exhibited the anticonvulsant effect against MES-induced seizures. However, baclofen when combined with sub-effective dose of pentobarbital 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 GABAA receptors, and activation of GABAB receptors alone does not seem to play any significant role in MES seizures and in the anticonvulsant effect of pentobarbital. However, activation of GABAB receptor does potentiate the facilitatory effect of barbiturates on GABAAergic 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 GABAAergic transmission.
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000818:Animals; D000927:Anticonvulsants; D001640:Bicuculline / Q000494:pharmacology; D004597:Electroshock; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010634:Phenobarbital / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010852:Picrotoxin; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology
D000596:Amino Acids; D021542:Amino Acids, Neutral; D000927:Anticonvulsants; D001640:Bicuculline; D009118:Muscimol; D010424:Pentobarbital; D010634:Phenobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; C013809:5-aminovaleric acid