Pharmaceutical Sciences Faculty Publications

Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A

Document Type

Article

Publication Date

12-2011

Journal Title

MedChemComm (Medicinal Chemistry Communications)

ISSN

2040-2503

Volume

2

Issue

12

First Page

1217

Last Page

1222

DOI

http://dx.doi.org/10.1039/c1md00192b

PubMed ID

22442751

PubMed Central® ID

PMC3307802

Abstract

Previous structure-activity relationship studies of salvinorin A have shown that modification of the acetate functionality off the C-2 position to a methoxy methyl or methoxy ethyl ether moiety leads to increased potency at KOP receptors. However, the reason for this increase remains unclear. Here we report our efforts towards the synthesis and evaluation of C-2 constrained analogs of salvinorin A. These analogs were evaluated at opioid receptors in radioligand binding experiments as well as in the GTP-γ-S functional assay. One compound, 5, was found to have affinity and potency at κ opioid (KOP) receptors comparable to salvinorin A. In further studies, 5 was found to attenuate cocaine-induced drug seeking behavior in rats comparably to salvinorin A. This finding represents the first example of a salvinorin A analog that has demonstrated anti-addictive capabilities.

Keywords

Medicine, therapeutics, hallucinogens, salvinorin A, anti-addictive

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