偏向性配体——阿片类镇痛药设计新思路

doi:10.3969/j.issn.2095-1396.2018.02.001

神经药理学报 ›› 2018, Vol. 8 ›› Issue (2): 1-7.DOI: 10.3969/j.issn.2095-1396.2018.02.001

• 专家论坛 • 下一篇

偏向性配体——阿片类镇痛药设计新思路

孙毅，谭博，苏瑞斌

抗毒药物与毒理学国家重点实验室，神经精神药理学北京市重点实验室，军事科学院军事医学研究院毒物药物研究所，北京，100850，中国

出版日期:2018-04-26 发布日期:2018-04-16
通讯作者: 谭博，男，助理研究员；研究方向：神经精神药理学；Tel：+86-010-66874604，E-mail：whutanbo@gmail.com 苏瑞斌，男，研究员；研究方向：神经精神药理学；Tel：+86-010-66931601，E-mail：ruibinsu@126.com
作者简介:孙毅，女，博士研究生；研究方向：神经精神药理学；Tel：+86-010-66874604，E-mail：surisun@yeah.net
基金资助:
国家自然科学基金项目（No. 81773709）

Biased Ligand——Novel Paradigm for Opioid Analgesics

SUN Yi，TAN Bo，SU Rui-bin

State Key Laboratory of Toxicology and Medical Countermeasures；Bei j ing Key Laboratory of Neuropsychopharmacology；Beijing Institute of Pharmacology and Toxicology，Beijing，100850，China

Online:2018-04-26 Published:2018-04-16
Contact: 谭博，男，助理研究员；研究方向：神经精神药理学；Tel：+86-010-66874604，E-mail：whutanbo@gmail.com 苏瑞斌，男，研究员；研究方向：神经精神药理学；Tel：+86-010-66931601，E-mail：ruibinsu@126.com
About author:孙毅，女，博士研究生；研究方向：神经精神药理学；Tel：+86-010-66874604，E-mail：surisun@yeah.net
Supported by:
国家自然科学基金项目（No. 81773709）

摘要/Abstract

摘要： 吗啡等阿片类药物作为镇痛药应用已有数百年历史，但其致呼吸抑制、耐受和成瘾等副作用限制了该类药物的使用，因此人们一直致力于寻找副作用更低的新型镇痛药。近年研究发现，μ阿片受体下游除了经典的G 蛋白依赖型通路外，还独立存在由β-arrestin 介导的信号通路，吗啡激活μ阿片受体产生的镇痛、镇静效应主要通过G 蛋白依赖型通路介导，而胃肠功能紊乱、呼吸抑制、耐受等副反应则由β-arrestin 依赖型通路介导。如果能发现只激活G 蛋白依赖型通路而不激活β-arrestin 依赖型通路的偏向性配体，就可能得到镇痛效应强而副作用低的化合物，这为设计新型强效、低副作用的阿片类镇痛药提供了新思路。该文将对μ阿片受体下游β-arrestin 依赖型信号通路及偏向性配体的发现、发展和应用进行综述。

关键词: 偏向性配体, &, mu, 阿片受体, 信号转导, 镇痛药

Abstract: Morphine and related opioids have been used as clinical analgesics for centuries，but various side effects-which include respiratory depression，tolerance and addictionset a limit to medication. Consequently，unremitting efforts have been directed towards the discovery of effective and nonlethal pain killers. Recent studies identified a novel β-arrestindependent pathway through μ-opioid receptor and indicated that side effects of morphine are mediated through β-arrestin-dependent pathway while G-protein-dependent pathway is thought to confer analgesia，which means biased ligands to G-protein signaling are possible analgesics without side effects. The theory of biased ligands may provide a novel strategy to design better and safer opioid analgesics. In this review，we summarized the discovery，development and application of β-arrestin-dependent pathway and biased ligands.

Key words: biased ligands, &, mu, opioid receptor, signal transduction, analgesic

中图分类号:

R964

孙毅，谭博，苏瑞斌. 偏向性配体——阿片类镇痛药设计新思路[J]. 神经药理学报, 2018, 8(2): 1-7.

SUN Yi，TAN Bo，SU Rui-bin. Biased Ligand——Novel Paradigm for Opioid Analgesics[J]. Acta Neuropharmacologica, 2018, 8(2): 1-7.

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偏向性配体——阿片类镇痛药设计新思路

Biased Ligand——Novel Paradigm for Opioid Analgesics

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