Kappa opioid receptor; Delta opioid receptor (KOR (for kappa opioid receptor), DOR (for delta opioid receptor))

The kappa opioid receptor (KOR) and delta opioid receptor (DOR) are both members of the G protein-coupled receptor (GPCR) superfamily that mediate the effects of endogenous opioid peptides (KOR: dynorphins; DOR: enkephalins) and a variety of synthetic opioid drugs[4][5][6][7]. KOR is predominantly found in the brain regions associated with aversion, diuresis, pain modulation, and neuroendocrine regulation[5][6][7]. DOR is distributed throughout the central and peripheral nervous system, playing a key role in modulating chronic and inflammatory pain, as well as exhibiting potential antidepressant and anxiolytic effects[1][2][4]. Both receptors are under active investigation as therapeutic targets, particularly for pain treatment without the severe side effects and abuse potential associated with mu opioid receptor targeting drugs[2][1][4]. KOR agonists are being developed as antipruritic, analgesic, and addiction-attenuating agents, while DOR agonists are under study for their unique analgesic and mood-modulating effects[2][1][4][7]. Both receptor classes pose challenges, including adverse CNS effects, tolerance, and pharmacological selectivity[1][4][6][7].

Other names

KOR (kappa opioid receptor)DOR (delta opioid receptor)Kappa receptorDelta receptor

Agonists of KOR and DOR inhibit neurotransmitter release by Gi/o protein-coupled inhibition of adenylate cyclase and decreased cAMP production, leading to reduced neuronal excitability, resulting in analgesia and other effects[5][6][4]. Antagonists block these effects, preventing the receptor-mediated modulation of pain and mood[7]. KOR and DOR activation leads to receptor internalization and, especially for DOR, lysosomal degradation or recycling which modulates receptor sensitivity and tolerance[4].