第一代和第二代组胺H_1受体拮抗剂对大鼠戊四唑点燃癫痫形成过程的作用比较  

Effects between the first-and second-generation histamine H_1-antagonists on seizure development of pentylenetetrazole -induced kindling in rats

作　　者：金春雷[1] 陈忠[1] 张力三[1] 郭谊[1] 张柳燕[1] 谷内一彦[2] 

机构地区：[1]浙江大学医学院药理学教研室,浙江杭州310031 [2]日本东北大学医学部药理教研室

出　　处：《浙江大学学报（医学版）》2004年第3期209-212,共4页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金( 30 3716 38);浙江省青年人才基金(R30 3779)资助项目

摘　　要：目的 :比较第一代组胺 H1受体拮抗剂苯海拉明和第二代拮抗剂索非那丁对大鼠戊四唑点燃癫痫形成过程的作用 ,并初步探讨其作用机制。方法 :大鼠隔日腹腔先注射不同代的 H1受体拮抗剂和 /或组氨酸 ,后注射亚惊厥剂量 ( 35 mg/ kg)的戊四唑 ,诱发化学性点燃癫痫 ,观察并比较各组每次戊四唑注射后 30 min内癫痫发作的行为变化。用荧光法测定脑内组胺含量。结果 :与对照组相比 ,苯海拉明 ( 5 mg/ kg)明显加速大鼠戊四唑化学点燃 ,而索非那丁 ( 5 mg/ kg)则不影响大鼠戊四唑点燃过程 ;苯海拉明加速戊四唑点燃的作用可被组胺的前体物质组氨酸所拮抗。结论 :第一代组胺 H1受体拮抗剂通过阻断脑内组胺 H1受体促进了戊四唑化学性点燃的形成 ,第二代组胺H1受体拮抗剂由于很难进入血脑屏障而无此作用。Objective: To investigate the effects and the mechanisms of the first-generation histamine H 1-antagonist diphenhydramine and the second-generation histamine H 1-antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats. Methods: The first- or second-generation histamine H 1-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically. Results: Compared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine. Conclusion: Seizure development of PTZ-induced kindling is promoted by the first- but not the second-generation histamine H 1-antagonists via the blockade of brain histamine H 1-receptor.

关 键 词：癫痫/化学诱导 疾病模型 动物 大鼠 苯海拉明/药理学 索非那丁/药理学 

分 类 号：R96[医药卫生—药理学]