Kappa-type opioid receptor (KOR) (KOR)

The Kappa-type opioid receptor (KOR) is a G protein-coupled receptor (GPCR) encoded by the OPRK1 gene, primarily expressed in the brain, spinal cord, and peripheral sensory neurons (UniProt P41145). It is one of the four major types of opioid receptors and is involved in the regulation of pain, stress, and emotional states (IUPHAR/BPS Guide to Pharmacology). Activation of KOR by endogenous ligands like dynorphins or exogenous agonists like nalbuphine typically results in analgesia and antipruritic effects (StatPearls, NBK545214). However, KOR activation is also notably associated with dysphoria and psychotomimetic side effects, which distinguishes it from the mu-opioid receptor (PubMed, PMID: 30102855). Nalbuphine specifically acts as a potent KOR agonist and a mu-opioid receptor antagonist, a profile used clinically to provide analgesia while minimizing mu-mediated side effects like respiratory depression (StatPearls, NBK545214). Beyond pain management, KOR is a therapeutic target for chronic itch and is being explored for its role in psychiatric disorders and addiction (PubMed, PMID: 31430498).

Other names

OPRK1Kappa opioid receptorKOR-1Opioid receptor kappa-1

Nalbuphine acts as an agonist at the kappa-type opioid receptor and as a partial agonist or antagonist at the mu-opioid receptor (StatPearls, NBK545214). Activation of the kappa-type opioid receptor coupled to Gi/Go proteins inhibits adenylyl cyclase, decreases cAMP levels, closes N-type voltage-gated calcium channels, and opens G protein-activated inwardly rectifying potassium (GIRK) channels, resulting in hyperpolarization and inhibition of neurotransmitter release (IUPHAR/BPS Guide to Pharmacology).