Kappa-type opioid receptor (KOR)

The kappa-type opioid receptor (KOR) is a member of the G protein-coupled receptor family that primarily binds the endogenous opioid peptide dynorphin. It is widely distributed throughout the central and peripheral nervous systems, where it plays a critical role in modulating pain, stress response, and mood. Unlike the mu-opioid receptor, which is associated with euphoria and high addiction potential, KOR activation is often associated with dysphoria and aversive states, making it a complex target for therapeutic intervention. In clinical practice, KOR agonists like difelikefalin are utilized for their potent anti-pruritic and analgesic properties, particularly in conditions where avoiding mu-opioid side effects like respiratory depression is necessary. Conversely, KOR antagonists are being investigated as potential treatments for depression and substance use disorders by blocking the negative affective states driven by dynorphin signaling. The development of peripherally restricted or biased agonists remains a key strategy to harness the receptor's therapeutic benefits while minimizing central nervous system side effects such as hallucinations.

Other names

Kappa opioid receptorKOPOPRK1Opioid receptor kappa 1K-OR

Activation of the kappa-type opioid receptor triggers Gi/o protein signaling, which inhibits adenylyl cyclase, reduces cyclic AMP levels, closes voltage-gated calcium channels, and opens inwardly rectifying potassium channels, leading to hyperpolarization and reduced neuronal excitability.