贝那替秦对最大电休克发作模型和戊四氮惊厥发作阈模型小鼠的抗惊厥作用  

Anticonvulsant effects of benactyzine on maximal electroshock seizure and pentetrazole seizure threshold test model mice

作　　者：陈小飞[1] 李建雄[2] 王永安[3] 

机构地区：[1]解放军总参谋部总医院药剂科,北京100091 [2]解放军总医院肿瘤内科,北京100853 [3]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学与毒理学杂志》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)~~

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.

关 键 词：贝那替秦 N-甲基-D-天冬氨酸 惊厥 

分 类 号：R965[医药卫生—药理学]