Advances in the structural understanding of opioid allostery

Trends Pharmacol Sci. 2025 Feb;46(2):98-101. doi: 10.1016/j.tips.2024.12.007. Epub 2025 Jan 17.

Abstract

Activation of the μ opioid receptor (MOR) can give analgesia, but also has dangerous side effects. Drugs that target MOR through an allosteric site, meaning they bind outside of the usual pocket, present a novel mode of receptor activation with different pharmacology relative to orthosteric drugs. Recent structural studies give valuable new information on how allosteric modulators interact with MOR.

Keywords: allostery; negative allosteric modulator; opioid; positive allosteric modulator; sodium binding site; μ-opioid receptor.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Analgesics, Opioid* / chemistry
  • Analgesics, Opioid* / pharmacology
  • Animals
  • Humans
  • Receptors, Opioid, mu* / agonists
  • Receptors, Opioid, mu* / chemistry
  • Receptors, Opioid, mu* / metabolism

Substances

  • Receptors, Opioid, mu
  • Analgesics, Opioid