Journal of Pharmacology and Experimental Therapeutics
August 1, 2006
Michael Ansonoff, Jiwen Zhang, Traci A Czyzyk et al.
101 citations
Salvia divinorum is a natural occurring hallucinogen that is traditionally used by the Mazatec Indians of central Mexico. The diterpene salvinorin A was identified as an active component of S. divinorum over 20 years ago, but only recently has biochemical screening indicated that a molecular target of salvinorin A in vitro is the kappa-opioid receptor. We have examined whether salvinorin A, the...
Bioorganic & Medicinal Chemistry Letters
June 15, 2006
Wayne W Harding, Matthew Schmidt, Kevin Tidgewell et al.
A synthetic sequence has been developed to selectively functionalize the furan ring of the natural product salvinorin A (2a). The synthetic routes described convert the furan ring in 2a into an N-sulfonylpyrrole, oxazole or an oxadiazole. In addition, a procedure has been found to remove the furan skeleton completely. Biological results indicate that replacement of the furan ring with an...
Australian Journal of Chemistry
June 13, 2006
Anthony R. Lingham, Helmut M. Hügel, Trevor J. Rook
Salvinorin A 1, a psychoactive neoclerodane diterpenoid from the Mexican sage S. divinorum, has gained interest as a selective ?-opioid receptor agonist. Non-racemic 3-furylamines 9a and 9b have been prepared from (+)-pseudoephedrine and (–)-ephedrine for application in the stereoselective synthesis of the ketone ring of 1. Diels–Alder reaction of 9b with methyl acrylate in aqueous media,...
Journal of Natural Products
June 2006
Kevin Tidgewell, Wayne W Harding, Anthony Lozama et al.
Several neoclerodanes, such as salvinorin A (1) and herkinorin (3), have recently been shown to possess opioid receptor activity in vitro and in vivo. To explore the structure-affinity relationships of this interesting class of compounds, we have synthesized a series of analogues from 1 isolated from Salvia divinorum. Here, we report the semisynthesis of neoclerodane diterpenes and their...
FEBS Journal
May 1, 2006
Brian E. Kane, Marcelo J. Nieto, Christopher R Mccurdy et al.
Salvinorin A is a potent kappa opioid receptor (KOP) agonist with unique structural and pharmacological properties. This non‐nitrogenous ligand lacks nearly all the structural features commonly associated with opioid ligand binding and selectivity. This study explores the structural basis to salvinorin A binding and selectivity using a combination of chimeric and single‐point mutant opioid...
Das Gesundheitswesen
May 1, 2006
Holger Siemann, Michael Specka, Fabrizio Schifano et al.
10 citations
The German pages of the Internet were searched for the presence of the hallucinogenic herbal drug Salvia divinorum, which is not dealt with in current addiction medicine or psychiatric text books. The investigation is part of the EU sponsored project "Psychonaut" as preparatory work for the development of an Internet-based early warning system. The first 100 websites of the search using "Salvia...
ChemInform
January 24, 2006
Bruce M Cohen, Et Al. Et Al.
AbstractFor Abstract see ChemInform Abstract in Full Text.
Arzneimittel-Forschung
2006
D Jeremy Stewart, Hesham Fahmy, Bryan L. Roth et al.
Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of 1 were developed and biologically evaluated in binding and functional assays. The C-2...
Journal of computer-aided molecular design
2006
Nidhi Singh, Gwénaël Chevé, David M Ferguson et al.
Combined ligand-based and target-based drug design approaches provide a synergistic advantage over either method individually. Therefore, we set out to develop a powerful virtual screening model to identify novel molecular scaffolds as potential leads for the human KOP (hKOP) receptor employing a combined approach. Utilizing a set of recently reported derivatives of salvinorin A, a structurally...
Journal of Pharmacology and Experimental Therapeutics
January 2006
William A Carlezon, Cécile Béguin, Jennifer A DiNieri et al.
Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of kappa-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A (SalvA), a potent and highly selective kappa-opioid...