在两种疼痛实验模型中，钾通道开放剂与吗啡表现出交叉耐受性。

Potassium channel openers exhibit cross-tolerance with morphine in two experimental models of pain.

作者信息

Khanna N, Malhotra R S, Mehta A K, Garg G R, Halder S, Sharma K K

机构信息

Department of Pharmacology, University College of Medical Sciences University College of Medical Sciences (University of Delhi) Delhi 110095, India.

出版信息

West Indian Med J. 2010 Oct;59(5):473-8.

PMID:21473392

Abstract

OBJECTIVE

The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa.

METHODS

Swiss albino mice of either gender weighing between 25-30 g were used for the study The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests.

RESULTS

The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers.

CONCLUSIONS

This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However such interaction occurs at the level of potassium channels rather than at the level of receptors.

摘要

目的

本研究旨在评估钾通道开放剂对吗啡耐受性的影响，以及反之亦然。

方法

使用体重在25 - 30克之间的雌雄瑞士白化小鼠进行研究。本研究采用福尔马林和甩尾试验，评估钾通道开放剂（克罗卡林、二氮嗪和米诺地尔）对吗啡耐受性的影响，以及反之亦然。

结果

在两种行为试验中，给吗啡耐受小鼠施用克罗卡林和米诺地尔时，其抗伤害感受作用均显著降低。然而，在福尔马林试验中观察到二氮嗪对吗啡耐受性的镇痛作用降低，但在甩尾试验中未观察到。当给长期用任何一种钾通道开放剂处理的动物施用吗啡时，观察到耐受性。当将吗啡注射到用吗啡与任何一种钾通道开放剂组合处理的组中时，观察到相同的效果。