偏向性阿片κ受体激动剂的研究进展

Recent advances of the κ opioid receptor agonists as biased signaling ligands

阿片κ受体是阿片受体的一种亚型,它与吗啡、哌替啶和芬太尼等阿片μ受体激动剂不同,阿片κ受体激动剂在具有强效镇痛活性的同时并不会产生成瘾、呼吸抑制和便秘等典型阿片样不良反应。但临床试验发现一些典型的κ受体激动剂会产生致幻、焦虑和镇静的不良反应,无法开发成为临床有用的镇痛药物。近年来,G蛋白偶联受体功能偏向性现象以及偏向性配基的发现为分离κ受体激动剂的镇痛药效与不良反应提供了新的思路。本文对偏向性κ受体激动剂及其潜在应用的最新进展进行了介绍和讨论。

Theκopioid receptor is a subtype of opioid receptors.Unlike typicalμopioid receptor agonists such as morphine and fentanyl,κopioid receptor agonists could produce potent analgesic effects without introduction of notorious opioid-like side effects such as addiction and respiratory depression.Unfortunately,theκopioid receptor agonists were associated with psychotic effects,such as hallucinations and anxiety,which made them unacceptable as useful clinical medications.With the advent of the era of biased signaling,it was hypothesized that the analgesic effects and unexpected psychotic effects could be disconnected to each other by design and discovery ofκopioid receptor agonists with a potential of biased signaling.In this review,the recent progress of biasedκopioid receptor agonists,as well as their potential clinical value,are introduced and discussed.