西咪替丁诱发小鼠癫痫发作。某些γ-氨基丁酸能药物的拮抗作用。

Cimetidine-induced seizures in mice. Antagonism by some GABAergic agents.

作者信息

Amabeoku G J, Chikuni O

机构信息

Department of Clinical Pharmacology, Medical School, University of Zimbabwe, Avondale, Harare.

出版信息

Biochem Pharmacol. 1993 Dec 14;46(12):2171-5. doi: 10.1016/0006-2952(93)90606-w.

DOI:10.1016/0006-2952(93)90606-w

PMID:8274150

Abstract

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.

摘要

在小鼠中研究了蝇蕈醇、氨氧乙酸（AOAA）、二氨基正丁酸（DABA）、巴氯芬、荷包牡丹碱、印防己毒素、士的宁、地西泮、苯巴比妥和苯妥英对西咪替丁诱导的癫痫发作的影响。西咪替丁（400 - 1000毫克/千克，腹腔注射）诱导剂量依赖性的强直性惊厥。蝇蕈醇、AOAA和DABA有效保护小鼠免受西咪替丁诱导的癫痫发作。荷包牡丹碱和印防己毒素显著增强西咪替丁诱导的癫痫发作，并有效拮抗蝇蕈醇、AOAA和DABA对癫痫发作的保护作用。地西泮和苯巴比妥显著保护小鼠免受西咪替丁诱导的癫痫发作，而苯妥英和士的宁对癫痫发作没有显著影响。这些结果表明，中枢γ-氨基丁酸神经传递的减弱可能是西咪替丁诱导小鼠癫痫发作的基础。