摘要
目的评价贝那替秦等抗胆碱药在不同惊厥模型的抗惊厥疗效,探讨其可能的作用机制。方法通过ig给予贝那替秦2-40 mg·kg^-1记录最大电休克发作模型（MES）及戊四氮惊厥发作阈模型（MST）模型小鼠的未出现惊厥数。制备新生Wistar小鼠海马神经元细胞,加入贝那替秦1-100μmol·L-1,MTT检测细胞存活率。结果贝那替秦2-40 mg·kg^-1在MES模型未出现惊厥数为2/10-7/10,在MST模型上未出现惊厥数为1/10-9/10均明显高于模型组（P〈0.05,P〈0.01）,2个模型的ED50分别为12.2（4.7-53.6）mg·kg^-1和12.5（7.0-25.9）mg·kg^-1。贝那替秦1-100μmol·L-1能明显对抗N-甲基-D-天冬氨酸（NMDA）对海马神经元的损伤作用,细胞存活率明显增加（P〈0.05）。结论贝那替秦在MES及MST惊厥模型均具明显抗惊厥作用,其作用机制可能与其对NMDA受体的拮抗作用有关。
OBJECTIVE To evaluate the anticonvulsant effect of benactyzine and other anticholinergic drugs on different seizure models and investigate their anti-seizure mechanism.METHODS Benactyzine 2-40 mg·kg^-1 were given ig to mice.The number of mice without convulsant appearance was recorded in the maximal electroshock seizure（MES） and pentetrazole（Metrazol） seizure threshold test（MST） model.Benactyzine 1-100 μmol·L^-1 was added to primary cultured hippocampus neurons,and the cell survival was detected by MTT assay.RESULTS The number of mice without convulsant appearance was 2/10-7/10 in the MES model vs 1/10-9/10 in MST model.The ED50 of benactyzine in MES model was 12.2（4.7-53.6）mg·kg-1 vs 12.5（7.5-25.9）mg·kg^-1 in the MST model.The cell survival in benactyzine 1-100 μmol·L^-1 group was significantly higher than that of N-methyl-D-aspartic acid（NMDA） model group（P〈0.05）.CONCLUSION Benactyzine shows significant anti-seizure effect on both MES and MST.The anticonvulsant mechanism might be related to its antagonism against NMDA receptors.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2011年第3期258-263,共6页
Chinese Journal of Pharmacology and Toxicology
基金
国家新药创制重大专项(2008ZXJ09002-003),国家新药创制重大专项(2008ZXJ09009-001)
国家自然科学基金资助项目(30400551),国家自然科学基金资助项目(30500682)~~
