第一代和第二代组胺H1受体拮抗剂对大鼠戊四唑点燃癫痫形成过程的作用比较

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.

Effects between the first- and second-generation histamine H1-antagonists on seizure development of pentylenetetrazole -induced kindling in rats

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.