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

@article{Roth2002SalvinorinAA,
  title={Salvinorin A: A potent naturally occurring nonnitrogenous $\kappa$ opioid selective agonist},
  author={Bryan L. Roth and Karen Baner and Richard B. Westkaemper and Daniel J. Siebert and Kenner C. Rice and SeAnna Steinberg and Paul R Ernsberger and Richard B. Rothman},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2002},
  volume={99},
  pages={11934 - 11939}
}
  • B. Roth, K. Baner, R. Rothman
  • Published 21 August 2002
  • Biology
  • Proceedings of the National Academy of Sciences of the United States of America
Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited 3H-bremazocine binding to cloned κ opioid receptors… 

Figures and Tables from this paper

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.

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).

The antinociceptive effect of salvinorin A in mice.

Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action

TLDR
The role of S. divinorum, SA and its analogues is explored, mainly on their analgesic and anti-inflammatory roles but also mention their psychoactive properties.

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

TLDR
These findings suggest that similarities in the pharmacological effects of salvinorin A and those of cannabinoids are mediated by its activation of KOR rather than by any direct action of salvia divinorum A on the endocannabinoid system.

The discriminative effects of the κ-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects

TLDR
These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at κ-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

Kappa-opioid receptor-mediated effects of the plant-derived hallucinogen, salvinorin A, on inverted screen performance in the mouse

TLDR
In the mouse, salvinorin A disrupted climbing behavior on an inverted screen task, indicating a rapid, but short-lived induction of sedation/motor incoordination and the possibility that the development of other diterpene-based opioids may yield important therapeutic compounds.
...

References

SHOWING 1-10 OF 90 REFERENCES

Salvia divinorum and the unique diterpene hallucinogen, Salvinorin (divinorin) A.

Salvia divinorum is a vision-inducing mint used by the Mazatec people of Oaxaca, Mexico. It is grown in California and other parts of the United States where it is employed as a legal hallucinogen.

Synthesis, opioid receptor binding, and biological activities of naltrexone-derived pyrido- and pyrimidomorphinans.

TLDR
A series of pyrido- and pyrimidomorphinans synthesized from naltrexone were evaluated for binding and biological activity at the opioid receptors, indicating the existence of a somewhat similar steric constraint at the ligand binding sites of delta, mu, and kappa receptors.

Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans

TLDR
The pharmacodynamic effects of enadoline significantly increased measures of sedation, confusion and dizziness, produced visual distortions and feelings of depersonalization, and increased urinary output, and the highest dose was not tolerated and led to psychotomimetic effects.

Salvinorin C, a new neoclerodane diterpene from a bioactive fraction of the hallucinogenic Mexican mint Salvia divinorum.

TLDR
Its structure was elucidated on the basis of extensive proton and C-13 NMR experiments, as well as by comparison of the NMR data with those of the mono- and diacetate derivatives 5-7 of the major NaBH(4)-reduction product of salvinorin A (2).

Novel opiate binding sites selective for benzomorphan drugs

TLDR
The data suggest that [3H]diprenorphine binds to a third subtype of opiate binding site, which has high affinity for diprenorphines but very low affinity for mu and delta agonists.
...