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Papers of the Week

Papers: 24 Sep 2022 - 30 Sep 2022

Pharmacology/Drug Development

2022 Sep 28

Annu Rev Pharmacol Toxicol

Biased Agonism: Lessons from Studies of Opioid Receptor Agonists.


Kelly E, Conibear A, Henderson G
Annu Rev Pharmacol Toxicol. 2022 Sep 28.
PMID: 36170657.


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. Expected final online publication date for the , Volume 63 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.