Receptor Pharmacology
Kappa-Opioid Receptor (KOR)
At-a-glance comparison
| Spec | Value |
|---|---|
| Receptor name | Kappa-opioid receptor (KOR; also OP2, KOP) |
| Encoding gene | OPRK1 (chromosome 8q11.23 in humans) |
| Receptor superfamily | G-protein-coupled receptor (GPCR), Class A (rhodopsin-like) |
| Primary signaling | Inhibitory G-protein (Gαi/o); β-arrestin recruitment as alternative pathway |
| Endogenous ligands | Dynorphin A, dynorphin B, big dynorphin |
| Reference exogenous agonists | U50,488; U69,593; salvinorin A (from Salvia divinorum) |
| Reference antagonists | Nor-binaltorphimine (nor-BNI), JDTic |
| Kratom alkaloid activity (in vitro) | Mitragynine and 7-OH: typically low affinity or weak antagonism in published assays |
What is the kappa-opioid receptor?
The kappa-opioid receptor is a G-protein-coupled receptor encoded by the gene OPRK1. It is one of the four classical opioid receptor subtypes and shares a conserved signaling architecture with the other opioid receptors. KOR is broadly distributed in the central and peripheral nervous systems and is the principal target of the endogenous dynorphin peptides - dynorphin A, dynorphin B, and big dynorphin.
KOR is the subject of extensive academic receptor-biology research. In published research models, KOR ligands and MOR ligands show distinct functional profiles, and this distinction is one reason KOR pharmacology has remained an active area of investigation even as selective KOR agonists have generally not advanced to broad clinical use.
Kratom alkaloids at the kappa-opioid receptor
In published in vitro work, mitragynine and 7-hydroxymitragynine typically show low binding affinity or weak antagonist activity at the kappa-opioid receptor. The receptor profile is distinct from the higher-affinity mu-opioid receptor partial agonism that characterizes both compounds. Mitragynine pseudoindoxyl shows a similar low-KOR-affinity profile in published assays.
The relative absence of meaningful KOR agonist activity in the principal kratom alkaloids is one of the receptor-pharmacology features that distinguishes them from full opioid agonists such as morphine, which has measurable affinity at multiple opioid receptor subtypes including KOR. As with other receptor profiles, these findings come from in vitro assays and should be interpreted as research-context observations only.
How KOR signals
When activated, KOR couples to inhibitory heterotrimeric G-proteins (Gi/o), reducing adenylate cyclase activity and modulating ion channels in a manner mechanistically similar to the other opioid receptors. β-Arrestin recruitment at KOR has been the subject of substantial investigation, and KOR-biased ligands have been studied in receptor-functional assays. Whether biased KOR signaling translates to distinct functional profiles in clinical settings is an active and unresolved question in receptor pharmacology.
Common questions about kappa-opioid receptor (kor)
- What does KOR stand for?
- KOR stands for Kappa-Opioid Receptor. The receptor is also referred to as OP2 in older pharmacological literature and KOP in some IUPHAR documents. The encoding gene is OPRK1.
- What gene encodes the kappa-opioid receptor?
- The OPRK1 gene, located on chromosome 8 (8q11.23) in humans.
- Are kratom alkaloids active at KOR?
- In published in vitro work, mitragynine and 7-hydroxymitragynine typically show low binding affinity or weak antagonist activity at KOR - distinct from their higher-affinity mu-opioid receptor partial agonism.
- What are the endogenous ligands at KOR?
- The dynorphin peptides - dynorphin A, dynorphin B, and big dynorphin - are the principal endogenous ligands at the kappa-opioid receptor.
- What is salvinorin A?
- Salvinorin A is a non-nitrogenous diterpene from the plant Salvia divinorum that is a selective and potent KOR agonist. It is the only well-characterized non-alkaloid agonist of any opioid receptor and is used as a research tool.
- Why does KOR pharmacology matter for kratom alkaloid research?
- Because the principal kratom alkaloids show low KOR activity, their overall opioid-receptor profile is concentrated at MOR (with weaker DOR antagonism) rather than spread across all opioid receptor subtypes. This MOR-concentrated profile is part of the pharmacological characterization that distinguishes kratom alkaloids from classical full opioid agonists.
Related glossary terms
References
- Bruchas MR, Land BB, Chavkin C. (2010). The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain Research.
- Varadi A, Marrone GF, Palmer TC, et al. (2016). Mitragynine/Corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism. J Med Chem. PMID 27513560.
- Roth BL, Baner K, Westkaemper R, et al. (2002). Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. PNAS.
- International Union of Basic and Clinical Pharmacology. Kappa-opioid receptor entry. https://www.guidetopharmacology.org
Important safety information:
Products containing 7-hydroxymitragynine (7-OH) are sold for adult use only (21+). These statements have not been evaluated by the U.S. Food and Drug Administration. Products are not intended to diagnose, treat, cure, or prevent any disease. The FDA has raised safety concerns regarding concentrated 7-OH products; consult a qualified healthcare professional before use. Do not operate vehicles or machinery after use. Keep out of reach of children and pets. Laws vary by state, buyers are responsible for knowing applicable law.