Synthesis and in vitro evaluation of salvinorin A analogues: effect of configuration at C(2) and substitution at C(18).
Cécile Béguin, Michele R Richards, Jian-Guo Li, Yulin Wang, Wei Xu, Lee-Yuan Liu-Chen, William A Carlezon, Bruce M Cohen
Bioorganic & Medicinal Chemistry Letters September 1, 2006 DOI: 10.1016/j.bmcl.2006.05.093 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Key points | C(2)-modified salvinorin derivatives acted as potent kappa-opioid agonists and are predicted to have improved metabolic stability (14a, 15a) or increased water solubility (10b). Preliminary structure-activity relationship analysis at C(18) suggests that this part of the molecule interacts with a tight lipophilic pocket of the kappa-receptor. |
Abstract
kappa-opioid receptor ligands have raised interest for their apparent effects on mood. The potent and selective kappa-agonist salvinorin A has short-lasting (15min) depressive-like effects in rats in behavioral models used to study mood disorders. Two series of salvinorin derivatives modified at C(2) and C(18), respectively, were synthesized and their kappa-opioid receptor affinities, potencies, and efficacies were evaluated using in vitro receptor binding and biochemical functional assays. Modification at C(2) yielded potent kappa-agonists that are predicted to have improved metabolic stability (14a, 15a) or increased water solubility (10b). Our preliminary SAR study at C(18) suggested that this part of the molecule interacts with a tight lipophilic pocket of the kappa-receptor.
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 33
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans. Neuroimage July 1, 2008
- Neo-clerodane diterpenes from the hallucinogenic sage Salvia divinorum. Journal of Natural Products December 1, 2006
- Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. Organic Letters April 3, 2008
- 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
and 28 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
- 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
- Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors. Biochemistry June 21, 2005
- Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates. Synapse December 1, 2005
- 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
and 7 more in the library