Kappa opioid receptor

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opioid receptor, kappa 1
Identifiers
SymbolOPRK1
Entrez4986
HUGO8154
OMIM165196
RefSeqNM_000912
UniProtP41145
Other data
LocusChr. 8 q11.2

The κ-Opioid receptors are a class of opioid receptors with dynorphins as the primary endogenous ligands, and ketazocine as a potent selective exogenous ligand. There are three variants: κ1, κ2, and κ3.

Effects

It has long been believed that kappa-opioid receptor agonists are dysphoric. This misconception traces back to early articles in the 1980s about human tests with κ-opioid receptor agonists. It was stated that:

"Both doses of ketocyclazocine substantially elevated scores on the LSD subscale of the ARCI as did the high dose of cyclazocine (fig. 2C). Morphine failed to increase scores significantly on this scale which measures dysphoria."[1]

It is now widely accepted that κ-opioid receptor (partial) agonists have hallucinogenic ("psychotomimetic") effects, as exemplified by salvinorin A. These effects are generally undesirable in medicinal drugs and could have had frightening or disturbing effects in the tested humans, but they are not per se dysphoric. It is thought that the hallucinogenic effects of drugs such as butorphanol, nalbuphine, and pentazocine serve to limit their opiate abuse potential. In the case of salvinorin A, a structurally novel neoclerodane diterpene κ-opioid receptor agonist, thes hallucinogenic effects are sought after. While salvinorin A is considered a hallucinogen, its effects are qualitatively different than those produced by the classical psychedelic hallucinogens such as LSD or mescaline. [2]

These receptors are involved with analgesia.

Kappa ligands are also known for their characteristic diuretic effects, due to their negative regulation of antidiuretic hormone (ADH).

Kappa agonism is neuroprotective against hypoxia/ischemia; as such, kappa receptors may represent a novel therapeutic target.

Location

κ receptors are located in the periphery by pain neurons, in the spinal cord and in the brain.

Reversal

Non-specific opioid receptor antagonists (e.g., naloxone) as well as the mixed opioid agonist/antagonist buprenorphine can be used to reverse the effects of kappa agonists.

References

  1. Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo J. Pharmacol. Exp. Ther. 238(3): 960-968 (1986) PMID 3018228
  2. Roth B, Baner K, Westkaemper R, Siebert D, Rice K, Steinberg S, Ernsberger P, Rothman R (2002). "Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist". Proc Natl Acad Sci U S A. 99 (18): 11934–9. PMID 12192085. link

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