Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents

@article{Walentiny2010KappaOM,
  title={Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents},
  author={David Matthew Walentiny and Robert Edward Vann and Jonathan A. Warner and L. S. King and Herbert H Seltzman and Hern{\'a}n A. Navarro and Charles E. Twine and Brian F Thomas and Anne F. Gilliam and Brian P. Gilmour and F. Ivy Carroll and Jenny L. Wiley},
  journal={Psychopharmacology},
  year={2010},
  volume={210},
  pages={275-284}
}
RationaleSalvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects.ObjectivesThis study represents a systematic examination of this hypothesis.MethodsSalvinorin A was isolated from S. divinorum and was evaluated in a battery of in vitro and in vivo procedures designed to detect… 

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

TLDR
Salvinorin A has therapeutic potential as a treatment for pain, mood and personality disorders, substance abuse, and gastrointestinal disturbances, and suggests that nonalkaloids are potential scaffolds for drug development for aminergic G-protein coupled receptors.

Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans

TLDR
Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans and rule out the involvement of a serotonin-2A-mediated mechanism.

Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes

TLDR
All psychoactive tryptamines are 5-HT2A agonists, but5-HT transporter (SERT) activity may contribute significantly to the pharmacology of certain compounds, and in vitro transporter data confirm structure-activity trends for releasers and uptake inhibitors whereby releasers tend to be structurally smaller compounds.

Investigating the Effects of Novel Kappa Opioid Receptor Agonists on the Dopamine Transporter

TLDR
Overall, this data demonstrates that KOPr rapidly regulates DAT function by a trafficking-independent, ERK1/2-, and lipid raft-dependent mechanism.

Salvinorin B derivatives, EOM-Sal B and MOM-Sal B, produce stimulus generalization in male Sprague-Dawley rats trained to discriminate salvinorin A

TLDR
The current findings are consistent with previous reports that salvinorin A produces detectable stimulus effects that are distinct from those of other drug classes and establish that synthetic derivatives of this substance produce similar discriminative stimulus effects.

References

SHOWING 1-10 OF 53 REFERENCES

The plant-derived hallucinogen, salvinorin A, produces κ-opioid agonist-like discriminative effects in rhesus monkeys

TLDR
The naturally occurring hallucinogen salvinorin A produces discriminative stimulus effects similar to those of a high efficacy κ-agonist in non-human primates.

Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.

  • B. RothK. Baner R. Rothman
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
Salvinorin A is the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist for kappa opioid receptors, and may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders).

Salvinorin A: A potent naturally occurring nonnitrogenous κ opioid selective agonist

  • B. RothK. Baner R. Rothman
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
Salvinorin A is the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist for κ opioid receptors and may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders).

Salvinorin A, an Active Component of the Hallucinogenic Sage Salvia divinorum Is a Highly Efficacious κ-Opioid Receptor Agonist: Structural and Functional Considerations

TLDR
Salvinorin A was found to be a full agonist, being significantly more efficacious than (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U69593) and similar in efficacy to dynorphin A (the naturally occurring peptide ligand for κ-opioid receptors).

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

TLDR
These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors, and future studies may assist in the development and screening of salvinegorin A analogs for potential pharmacotherapy.

Involvement of κ-Opioid and Endocannabinoid System on Salvinorin A-Induced Reward

Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward.

TLDR
These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-opioid and (endo)cannabinoid system in rats.

Cannabinoid pharmacological properties common to other centrally acting drugs.

Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement

TLDR
Results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior.
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