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.
Comparable studies
Other experimental studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. | 2002 | Experimental study | |
| Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Cloned human kappa-opioid receptors expressed in human embryonic kidney-293 cells and... | 2004 | Experimental study | |
| Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Animal model | 2014 | Experimental study | |
| Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors. | 2005 | Experimental study | |
| Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Rat brain striatum homogenates | 2009 | Laboratory experiment |
Citations in the library
Cited by 17
- Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Journal of Medicinal Chemistry December 26, 2014
- Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents. Molecules October 11, 2018
- Neoclerodanes as atypical opioid receptor ligands. Journal of Medicinal Chemistry May 9, 2013
- Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs. Frontiers in Psychiatry 2019
- Salvinorin a and related compounds as therapeutic drugs for psychostimulant-related disorders. Current Drug Abuse Reviews 2014
and 12 more in the library
Cites 17
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum The Journal of Organic Chemistry November 1, 1984
- Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). Journal of Ethnopharmacology May 1, 1983
- Salvia divinorum and the unique diterpene hallucinogen, Salvinorin (divinorin) A. Journal of Psychoactive Drugs 1994
and 12 more in the library