Biased agonism at kappa opioid receptors: Implication in pain and mood disorders

Eur J Pharmacol. 2015 Sep 15;763(Pt B):184-90. doi: 10.1016/j.ejphar.2015.07.018. Epub 2015 Jul 8.


The kappa opioid receptor (k receptor) and its endogenous ligand dynorphin have received significant attention due to their involvement in pathophysiology of mood disorders, drug addiction, psychotic disorders and pain. Multiple lines of evidences suggest that the k receptor modulates overlapping neurocircuits connecting brainstem monoaminergic nuclei with forebrain limbic structures and thereby regulates neurobiological effects of stress and psychostimulants. The emerging concept of "biased agonism" (also known as functional selectivity) for G Protein Coupled Receptor (GPCR) ligands have provided new insights into overall response generated by a ligand, which could be exploited for drug discovery. According to this concept, every ligand possesses the unique ability (coded in its structure) that dictates distinct signalling pattern, and consequently beneficial or adverse response. Although still a long way to comprehend the clinical potential of biased GPCR ligands, such ligand could be vital pharmacological probes. This article highlights various lines of evidence, which indicates different ligands of k receptor as "biased", and their potential implications in mood and pain disorders.

Keywords: Biased agonism; Dynorphin; Kappa opioid receptor; Mood disorders; Opioid receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Humans
  • Ligands
  • Mood Disorders / drug therapy
  • Mood Disorders / metabolism*
  • Pain / drug therapy
  • Pain / metabolism*
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / metabolism*
  • Substrate Specificity


  • Ligands
  • Receptors, Opioid, kappa