Salvinorin A is a psychoactive natural product that has been found to be a potent and selective kappa opioid receptor agonist in vitro and in vivo. The activity of salvinorin A is unusual compared to other opioids such as morphine in that it mediates potent kappa opioid receptor signaling yet leads to less receptor downregulation than observed with other kappa agonists. Our initial chemical...
Salvinorin A [(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2h-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester] is a hallucinogenic kappa-opioid receptor agonist that lacks the usual basic nitrogen atom present in other known opioid ligands. Our first published studies indicated that Salvinorin A weakly inhibited mu-receptor binding, and...
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...
Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and is the first example of a non-nitrogenous opioid receptor ligand. At present, there is little information available as to why this compound is selective for kappa opioid receptors. One approach to better understanding the mode of binding of 1 at kappa receptors...
Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8...
[reaction: see text] Two new neoclerodane diterpenes, salvinicins A (4) and B (5), were isolated from the dried leaves of Salvia divinorum. The structures of these compounds were elucidated by spectroscopic techniques, including (1)H and (13)C NMR, NOESY, HMQC, and HMBC. The absolute stereochemistry of these compounds was assigned on the basis of single-crystal X-ray crystallographic analysis...