Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of Opioid Receptor affinity.
Gianfranco Fontana, Giuseppe Savona, Benjamín Rodríguez, Christina M Dersch, Richard B Rothman, Thomas E Prisinzano
Tetrahedron December 20, 2008 DOI: 10.1016/j.tet.2008.08.043 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Salvia splendens Salvia family Salvia genus Plant compounds Plant investigation Opioid receptors Kappa-opioid agonist Kappa receptors Opioid interactions Receptor binding Drug discovery Natural products Phytochemistry Plant-derived compounds Natural compounds Ethnopharmacology Pyrazoline structure Chemical scaffolds Synthetic compounds |
| Citations | 32 |
| Key findings | None of the tested compounds from Salvia splendens or semisynthetic derivatives showed high-affinity binding to human opioid receptors, though one compound showed modest kappa receptor affinity. |
Abstract
Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific kappa-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens (2 - 8) together with a series of semisynthetic derivatives (9 - 24), some of which possess a pyrazoline structural moiety (9, 19 - 22), have been tested for affinity at human mu, delta, and kappa opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for kappa receptors suggesting other naturally neoclerodanes from different Salvia species may possess opioid affinity.
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 9
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A. MedChemComm December 1, 2011
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A. Journal of Natural Products April 25, 2011
- Semisynthetic neoclerodanes as kappa opioid receptor probes. Bioorganic & Medicinal Chemistry May 1, 2012
and 4 more in the library
Cites 8
- Salvinorin A: allosteric interactions at the mu-opioid receptor. Journal of Pharmacology and Experimental Therapeutics February 1, 2007
- Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway. Phytochemistry July 1, 2007
- Isolation and chemical modification of clerodane diterpenoids from Salvia species as potential agonists at the kappa-opioid receptor. Chemistry & Biodiversity July 1, 2007
- Synthetic studies of neoclerodane diterpenes from Salvia divinorum: selective modification of the furan ring. Bioorganic & Medicinal Chemistry Letters June 15, 2006
- Synthesis and in vitro pharmacological studies of C(4) modified salvinorin A analogues. Bioorganic & Medicinal Chemistry Letters October 1, 2005
and 3 more in the library