氟桂利嗪对戊巴比妥钠睡眠的增强作用  

Potentiating effect of flunarizine on pentobarbital sleep

作　　者：师晓荣[1] 张英俊[2] 王黎恩[1] 崔素颖[1] 崔翔宇[1] 杜楠[1] 张帆[1] 张永鹤[1] 

机构地区：[1]北京大学医学部基础药理系,北京100191 [2]吉林石化总医院,吉林省吉林市132022

出　　处：《中国药理学通报》2009年第3期335-340,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30772556,30640070);杨森研究基金会研究基金;北京大学国家“985”资助项目

摘　　要：目的探讨钙通道阻断剂氟桂利嗪对戊巴比妥钠催眠作用的影响及其可能的机制。方法采用翻正反射试验和大鼠脑电分析作为观察指标,分别考查对阈上剂量戊巴比妥钠诱导的小鼠睡眠时间和阈下剂量戊巴比妥钠诱导小鼠入睡率以及睡眠时相的作用。结果氟桂利嗪不仅可以剂量依赖性地延长阈上剂量戊巴比妥钠(45mg·kg-1,ip)诱导的小鼠睡眠时间,而且还可以提高阈下剂量戊巴比妥钠(28mg·kg-1,ip)诱导的小鼠入睡率。左旋多巴(L-DOPA)可明显减少阈上戊巴比妥钠诱导的小鼠睡眠时间,而氟桂利嗪可逆转此作用。脑电分析结果表明,氟桂利嗪不仅可以增加大鼠睡眠时间,而且还可增加非快眼动睡眠(NREMs)和快眼动睡眠(REMs)时间,而在NREMs期,主要延长深睡眠(SWS)时间,对浅睡眠(Light)时间没有影响。氟桂利嗪对T型和L型钙通道均具有阻断作用,而L型钙通道激动剂〔(S)-(-)-BAYK8644〕对氟桂利嗪增强戊巴比妥钠催眠作用未显示其拮抗作用。结论氟桂利嗪可增强戊巴比妥钠的催眠作用,该作用主要是通过其T型钙通道阻断作用而实现的,其作用机制可能与多巴胺能神经系统相关。Aim To investigate the effect of flunarizine on pentobarbital sleep and it＇s possible mechanism. Methods Righting Reflex test and EEG analysis methods were used. Results Flunarizine significantly potentiated pentobarbital hypnosis by increasing sleep time which induced by hypnotic dose of pentobarbital （45 mg ·kg^-1, ip） and the sleep onset induced by sub-hypnotic dosage of pentobarbital （28 mg·kg^-1, ip） in mice. Meanwhile, flunarizinc significantly increased both NREM and REM sleep time, and during NREMs SWS was increased significantly in pentobarbital treated rats. Pretreatment of L-DOPA significantly suppressed pentobarbital hypnosis and flunarizine significantly reversed this effect. Flunarizine is known as a mixed T-and L-type Ca^2＋ channel blocker. In the present study, the potentiating effect of flunarizine on pentobarbital sleep was not blocked by BAY K8644, an L-type Ca^2＋ channel agonist. Conclusion The augmentative effect of flunarizine on pentobarbital-induced sleep may be mainly through its T-type Ca^2＋ channel blocking property and may be related to dopaminergic system at least in part.

关 键 词：氟桂利嗪 戊巴比妥钠睡眠 左旋多巴 BAY K 8644 

分 类 号：R-332[医药卫生] R338.63