Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A.
Katherine M Prevatt-Smith, Kimberly M Lovell, Denise S Simpson, Victor W Day, Justin T Douglas, Peter J Bosch, Christina M Dersch, Richard B Rothman, Bronwyn M Kivell, Thomas E Prisinzano
MedChemComm December 1, 2011 DOI: 10.1039/C1MD00192B (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Intervention | Salvinorin A |
| Topics | Salvia divinorum |
| Keywords | Drug addiction treatment Treating drug addiction Anti-addictive capabilities Therapeutic benefits Reduced cocaine-induced drug-seeking Medicinal chemistry Modified compound Structural changes Synthesizing New versions Specific analog Pharmacology Potency Key brain receptors Opioid receptors Interaction Evaluating Hallucinogen derivatives Natural hallucinogen |
| Citations | 50 |
| Key findings | Compound 5, a C-2 constrained analog of salvinorin A, has affinity and potency at KOP receptors comparable to salvinorin A and attenuates cocaine-induced drug seeking behavior in rats. |
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.