二苯甲基哌嗪对大鼠最大电休克惊厥的抗惊厥作用。

Anticonvulsant effects of benzhydryl piperazines on maximal electroshock seizures in rats.

作者信息

Novack G D, Stark L G, Peterson S L

出版信息

J Pharmacol Exp Ther. 1979 Mar;208(3):480-4.

Abstract

The anticonvulsant effects of four benzhydryl piperazines, SC-13504 (ropizine, an anticonvulsant), hydroxyzine (HDX, an anxiolytic), chlorcyclizine (CCZ, an antihistaminic) and buclizine (BUC, an antihistaminic), were investigated utilizing a modified maximal electroshock seizure test in rats. In addition to detecting the presence or absence of tonic hindlimb extension, the modified method quantified various phases of the seizure. All four benzhydryl piperazines exhibited anticonvulsant activity in maximal electroshock seizure, but SC-13504 was similar in efficacy to phenobarbital and phenytoin, and much more effective than HDX, CCZ or BUC. Additionally, SC-13504 possessed a therapeutic index much greater than any of the compounds tested. The duration of action of the benzhydryl piperazines, in hours was: SC-13504, 0.5 to 8; HDX, 0.5 to 2; CCZ, 0.5 to 16; and BUC, 2 to 8. Buc and CCZ are postulated to be converted to active anticonvulsant metabolites.

摘要

利用改良的大鼠最大电休克惊厥试验，研究了四种二苯甲基哌嗪（抗惊厥药SC - 13504（罗哌嗪）、抗焦虑药羟嗪（HDX）、抗组胺药氯环利嗪（CCZ）和抗组胺药布克利嗪（BUC））的抗惊厥作用。除了检测强直性后肢伸展的有无外，改良方法还对惊厥的各个阶段进行了量化。所有四种二苯甲基哌嗪在最大电休克惊厥试验中均表现出抗惊厥活性，但SC - 13504的疗效与苯巴比妥和苯妥英相似，且比HDX、CCZ或BUC有效得多。此外，SC - 13504的治疗指数远高于所测试的任何化合物。二苯甲基哌嗪的作用持续时间（以小时计）为：SC - 13504，0.5至8；HDX，0.5至2；CCZ，0.5至16；BUC，2至8。推测BUC和CCZ会转化为具有活性的抗惊厥代谢物。