Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Jan 27;48(2):345-8.
doi: 10.1021/jm049438q.

Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist

Thomas A Munro  1 , Mark A Rizzacasa, Bryan L Roth, Beth A Toth, Feng Yan
Affiliations

Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist

Thomas A Munro et al. J Med Chem. .

Abstract

Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective kappa opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
a Reagents: (a) H2 (1 atm), Pd/C (5%), MeOH, rt; (b) H2 (4 atm), Rh/C (5%), CH2Cl2/MeOH, rt; (c) DIBALH, THF, -78 °C; (d) Et3SiH, BF3•Et2O, CH2Cl2, 0 °C.
Scheme 2
Scheme 2
a Reagents: (a) LiSEt, DMPU, 55 °C; (b) Ac2O, DMAP, pyridine, rt; (c) BH3, THF, 55 °C; (d) Thiocarbonyldiimidazole, DMF, 90 °C; (e) Bu3SnH, AIBN, toluene, 80 °C.
Figure 1
Figure 1
See this image and copyright information in PMC

References

    1. Ortega A, Blount JF, Manchand PS. Salvinorin, a New trans-Neoclerodane Diterpene from Salvia divinorum (Labiatae) J. Chem. Soc., Perkin Trans. 1. 1982:2505–2508.
    1. Siebert DJ. Salvia divinorum and salvinorin A: New pharmacologic findings. J. Ethnopharmacol. 1994;43:53–56. - PubMed
    1. Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB. Salvinorin A: A potent naturally occurring nonnitrogenous κ opioid selective agonist. Proc. Natl. Acad. Sci. U.S.A. 2002;99:11934–11939. - PMC - PubMed
    1. Chavkin C, Sud S, Jin W, Stewart J, Zjawiony JK, Siebert DJ, Toth BA, Hufeisen SJ, Roth BL. Salvinorin A, an Active Component of the Hallucinogenic Sage Salvia divinorum Is a Highly Efficacious κ-Opioid Receptor Agonist: Structural and Functional Considerations. J. Pharmacol. Exp. Ther. 2004;308:1197–1203. - PubMed
    1. Delvaux M. Pharmacology and clinical experience with fedotozine. Expert Opin. Investig. Drugs. 2001;10:97–110. - PubMed

Publication types