CIMETIDINE-INDUCED SEIZURES IN MICE - ANTAGONISM BY SOME GABAERGIC AGENTS

The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine induced seizures were stud ied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DABA effectively protected mice a gainst cimetidine-induced seizures. Bicuculline and picrotoxin signifi cantly potentiated the seizures induced by cimetidine and effectively antagonized the protective e:ffects of muscimol, AOAA and DABA against the seizures. Diazepam and phenobarbitone significantly protected the mice against cimetidine-induced seizures while phenytoin and strychni ne did not significantly alter the seizures. These results indicate th at the attenuation of central gamma-aminobutyric acid neurotransmissio n may underlie cimetidine-induced seizures in mice.