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 studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DABA effectively protected mice against cimetidine-induced seizures. Bicuculline and picrotoxin significantly potentiated the seizures induced by cimetidine and effectively antagonized the protective effects of muscimol, AOAA and DABA against the seizures. Diazepam and phenobarbitone significantly protected the mice against cimetidine-induced seizures while phenytoin and strychnine did not significantly alter the seizures. These results indicate that the attenuation of central gamma-aminobutyric acid neurotransmission may underlie cimetidine-induced seizures in mice.
Amabeoku
G J
GJ
Department of Clinical Pharmacology, Medical School, University of Zimbabwe, Avondale, Harare.
Chikuni
O
O
D000613:Aminobutyrates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002927:Cimetidine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control; D013331:Strychnine / Q000494:pharmacology
D000613:Aminobutyrates; D000625:Aminooxyacetic Acid; D001418:Baclofen; D001640:Bicuculline; D002927:Cimetidine; D003975:Diazepam; D009118:Muscimol; D010634:Phenobarbital; D010672:Phenytoin; D010852:Picrotoxin; D018079:Receptors, GABA; D013331:Strychnine; C005959:2,4-diaminobutyric acid