Send to

Choose Destination
Br J Pharmacol. 2015 Jan;172(2):287-96. doi: 10.1111/bph.12600. Epub 2014 Jul 1.

Novel GPCR paradigms at the μ-opioid receptor.

Author information

Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia.


Opioids, such as morphine, are the most clinically useful class of analgesic drugs for the treatment of acute and chronic pain. However, the use of opioids is greatly limited by the development of severe adverse side effects. Consequently, drug discovery efforts have been directed towards improving the therapeutic profile of opioid-based treatments. Opioid receptors are members of the family of GPCRs. As such, the recent GPCR paradigms of biased agonism and allosterism may provide novel avenues for more effective analgesics. Biased agonism (or functional selectivity) has been described for all the opioid receptor family members. Furthermore, the first allosteric modulators of opioid receptors have very recently been described. However, identification and quantification of biased agonism in a manner that is informative to medicinal chemists and drug discovery programmes still remains a challenge. In this review, we examine the progress, to date, towards identification and quantification of biased agonism and allosterism at the μ-opioid receptor in the context of its implications for the discovery of better and safer analgesics.


This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit


GPCR; allosterism; biased-agonism; μ-opioid receptor

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center