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Papers of the Week

Papers: 8 Jun 2019 - 14 Jun 2019

Pharmacology/Drug Development

2019 Nov

Mol Pharmacol



A biased view of µ opioid receptors?


Conibear AE, Kelly E
Mol Pharmacol. 2019 Nov; 96(5):542-549.
PMID: 31175184.


The field of biased agonism has grown substantially in recent years and the μ opioid receptor has been one of the most intensively studied receptor targets for developing biased agonists. Yet, despite extensive research efforts the development of analgesics with reduced adverse effects remains a significant challenge. In this review we discuss the evidence to support the prevailing hypothesis that a G protein biased agonist at the μ opioid receptor would be an effective analgesic without the accompanying adverse effects associated with conventional μ opioid agonists. We also assess the current status of established and novel μ opioid receptor ligands that are proposed to be biased ligands. SIGNIFICANCE STATEMENT: The idea that biased agonists at the &[mu] opioid receptor might provide a therapeutic advantage in terms of producing effective analgesia but with fewer adverse effects has driven the design of novel G protein-biased agonists. However is the desirability of G protein-biased agonists at &[mu] opioid receptor substantiated by what we know of the physiology and pharmacology of the receptor? Also do any of the novel biased agonists live up to their initial promise? Here we address these issues by critically examining the evidence that G protein bias really is desirable and also by discussing whether the ligands so far developed are clearly biased in vitro and whether this produces responses in vivo that might be commensurate with such bias.