Modification of the furan ring of salvinorin A: identification of a selective partial agonist at the kappa opioid receptor.
Cécile Béguin, Katharine K Duncan, Thomas A Munro, Douglas M Ho, Wei Xu, Lee-Yuan Liu-Chen, William A Carlezon, Bruce M Cohen
Bioorganic & Medicinal Chemistry February 1, 2009 DOI: 10.1016/j.bmc.2008.12.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Key points | Modifying the furan ring and C-13 position of salvinorin A yields KOPR-selective compounds with varied activity: 12-epi-salvinorin A is a selective partial agonist, small C-13 esters and ethers are weak agonists, C-13 amides are inactive, and oxadiazole substitution abolishes KOPR affinity. None of the compounds antagonized KOPR or bound mu or delta opioid receptors. |
Abstract
In an effort to find novel agents which selectively target the kappa opioid receptor (KOPR), we modified the furan ring of the highly potent and selective KOPR agonist salvinorin A. Introduction of small substituents at C-16 was well tolerated. 12-epi-Salvinorin A, synthesized in four steps from salvinorin A, was a selective partial agonist at the KOPR. No clear SAR patterns were observed for C-13 aryl ketones. Introducing a hydroxymethylene group between C-12 and the furan ring was tolerated. Small C-13 esters and ethers gave weak KOPR agonists, while all C-13 amides were inactive. Finally, substitution of oxadiazoles for the furan ring abolished affinity for the KOPR. None of the compounds displayed any KOPR antagonism or any affinity for mu or delta opioid receptors.
Comparable studies
Other theoretical and historical papers on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. | 2008 | Theoretical or philosophical paper | |
| The claustrum's proposed role in consciousness is supported by the effect and target localization of Salvia divinorum. | 2014 | Theoretical or philosophical paper | |
| Total Synthesis of (-)-Salvinorin A. | 2016 | Theoretical or philosophical paper | |
| Salvia Divinorum: entrSalvia divinorum: Entre la prohibición y la construcción de su conocimientoe a proibição e a construção do seu saber | 2022 | Theoretical or philosophical paper | |
| Salvia divinorum induces body awareness changes comparable to metamorphic symptoms in the Alice in Wonderland syndrome | 2019 | Theoretical or philosophical paper |
Citations in the library
Cited by 22
- Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Journal of Medicinal Chemistry December 26, 2014
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A. Journal of Natural Products April 25, 2011
- Salvia divinorum use and phenomenology: results from an online survey. Journal of Psychopharmacology November 1, 2011
- Semisynthetic neoclerodanes as kappa opioid receptor probes. Bioorganic & Medicinal Chemistry May 1, 2012
and 17 more in the library
Cites 12
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Psychopharmacology March 1, 2004
- Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. Organic Letters April 3, 2008
- Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A. Journal of Natural Products 2006
- The Absolute Stereochemistry of Salvinorins Chemistry Letters November 1, 1990
and 7 more in the library