化学惊厥剂与抗惊厥剂之间的体内相互作用分析。

An analysis of the in vivo interactions between chemical convulsants and anticonvulsants.

作者信息

Coleman J C, Shenoy A K, Chweh A Y, Swinyard E A

出版信息

Life Sci. 1985 Aug 26;37(8):749-55. doi: 10.1016/0024-3205(85)90545-4.

Abstract

The interactions between pentylenetetrazol (PTZ), picrotoxin (PIC), or bicuculline (BIC) and diazepam, phenobarbital, or valproate were subjected to Schild plot analysis. Log dose-probit response curves for minimal clonic seizures were determined for three chemical convulsants in the absence and in the presence of various concentrations of three anticonvulsants. The calculated median convulsant doses were subjected to Schild plot analysis and the pA2 values determined. A comparison of the pA2 values for the various convulsant/anticonvulsant combinations suggested the following conclusions: (i) the sequence of events leading to minimal clonic seizures evoked by PTZ or PIC involves a common receptor, (ii) BIC acts through a different receptor, and (iii) Schild plot analysis of the antagonism between convulsant and anticonvulsant is in agreement with their antagonism in vitro studies. Thus, Schild plot analysis can be useful in the evaluation of anticonvulsant activity in vivo and may offer some insight into the potential clinical usefulness of anticonvulsant substances.

摘要

对戊四氮（PTZ）、印防己毒素（PIC）或荷包牡丹碱（BIC）与地西泮、苯巴比妥或丙戊酸盐之间的相互作用进行了希尔德分析。在不存在和存在不同浓度的三种抗惊厥药的情况下，测定了三种化学惊厥剂诱发最小阵挛性惊厥的对数剂量-概率反应曲线。对计算出的半数惊厥剂量进行希尔德分析并确定pA2值。对各种惊厥剂/抗惊厥剂组合的pA2值进行比较得出以下结论：（i）导致PTZ或PIC诱发最小阵挛性惊厥的事件序列涉及共同受体；（ii）BIC通过不同受体起作用；（iii）惊厥剂与抗惊厥剂之间拮抗作用的希尔德分析与其体外拮抗研究结果一致。因此，希尔德分析可用于评估体内抗惊厥活性，并可能为抗惊厥物质的潜在临床应用提供一些见解。