Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics

Michael Remesic, Victor J. Hruby, Frank Porreca, Yeon Sun Lee

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest. It has been shown that allosteric modulators play key roles in influencing receptor function such as its tolerance to a ligand and affect downstream pathways. There has been a high variance of chemical structures that provide allosteric modulation at a given receptor, but recent studies and reviews tend to focus on the altered cellular mechanisms instead of providing a more rigorous description of the allosteric ligand's structure-function relationship. In this review, we aim to explore recent developments in the structural motifs that potentiate orthosteric binding and their influences on cellular pathways in an effort to present novel approaches to opioid therapeutic design.

Original languageEnglish (US)
Pages (from-to)1147-1158
Number of pages12
JournalACS Chemical Neuroscience
Issue number6
StatePublished - Jun 21 2017


  • Allosteric modulation
  • Cannabinoid receptors
  • Heterodimers
  • Opioid receptors
  • Opioid side effects
  • Pain therapeutics
  • Sigma receptors

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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