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Papers of the Week

Papers: 8 Feb 2020 - 14 Feb 2020

Animal Studies, Pharmacology/Drug Development

2020 Feb 12

Br J Pharmacol

Morphine-induced respiratory depression is independent of ß-arrestin2 signalling.


Kliewer A, Gillis A, Hill R, Schmidel F, Bailey C, Kelly E, Henderson G, Christie MJ, Schulz S
Br J Pharmacol. 2020 Feb 12.
PMID: 32052419.


G protein-coupled receptors can signal through both G proteins and ß-arrestin2. For the μ-opioid receptor, early experimental evidence from a single study suggested that G protein signalling mediates analgesia whereas ß-arrestin2 signalling mediates respiratory depression and constipation. Consequently, for more than a decade much research effort has been focused on developing biased μ-opioid agonists that preferentially target G protein signalling over β-arrestin signalling as it was believed that such drugs would be analgesics devoid of respiratory depressant activity. However, the prototypical compounds that have been developed based on this concept have so far failed in clinical and preclinical development.