Biased Agonism: Lessons from Studies of Opioid Receptor Agonists.

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI:10.1146/annurev-pharmtox-052120-091058
Eamonn Kelly, Alexandra Conibear, Graeme Henderson
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引用次数: 14

Abstract

In ligand bias different agonist drugs are thought to produce distinct signaling outputs when activating the same receptor. If these signaling outputs mediate therapeutic versus adverse drug effects, then agonists that selectively activate the therapeutic signaling pathway would be extremely beneficial. It has long been thought that μ-opioid receptor agonists that selectively activate G protein- over β-arrestin-dependent signaling pathways would produce effective analgesia without the adverse effects such as respiratory depression. However, more recent data indicate that most of the therapeutic and adverse effects of agonist-induced activation of the μ-opioid receptor are actually mediated by the G protein-dependent signaling pathway, and that a number of drugs described as G protein biased in fact may not be biased, but instead may be low-intrinsic-efficacy agonists. In this review we discuss the current state of the field of bias at the μ-opioid receptor and other opioid receptor subtypes.

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偏倚激动作用:阿片受体激动剂研究的启示。
在配体偏倚中,当激活同一受体时,不同的激动剂药物被认为产生不同的信号输出。如果这些信号输出介导治疗与不良药物效应,那么选择性激活治疗信号通路的激动剂将是非常有益的。长期以来,人们一直认为μ-阿片受体激动剂可以选择性地激活G蛋白-过β-抑制蛋白依赖的信号通路,从而产生有效的镇痛效果,而不会产生呼吸抑制等副作用。然而,最近的数据表明,大多数激动剂诱导的μ-阿片受体激活的治疗和不良反应实际上是由G蛋白依赖的信号通路介导的,并且一些被描述为G蛋白偏倚的药物实际上可能不是偏倚的,而可能是低内在功效的激动剂。本文综述了μ-阿片受体和其他阿片受体亚型的偏倚研究现状。
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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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