Salvinorin (Sal) A is a naturally occurring, selective kappa opioid receptor (KOPR) agonist with a short duration of action in vivo. Pharmacological properties of a C(2) derivative, 2-methoxymethyl (MOM)-Sal B, were characterized. MOM-Sal B bound to KOPR with high selectivity and displayed approximately 3-fold higher affinity than U50,488H...
Novel semisynthetic analogs of salvinorin A, a full agonist having extraordinary affinity as well as selectivity for the κ-opioid receptor (KOR), were obtained in good yields. The derivatives are remarkable for their unusual and unique hemiacetal structure in the salvinorin series of compounds. The formation of the hemiacetal occurs with epimerization at C-12, thus preserving the original...
The recreational drug, Salvinorin A, derived from the plant of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. The abuse of selective k-agonists is a novel phenomenon, the mechanism of which is not fully understood. We investigated salvinorin A given SC on the conditioned place preference (.05-160 microg/kg) and intracerebroventricular (ICV) self-administration (.01-1...
The hallucinogenic plant Salvia divinorum has been used for medical treatments of gastrointestinal disorders. Here, we evaluated the effect of a standardized extract from the leaves of Salvia divinorum (SDE) and of its active ingredient salvinorin A on motility in vivo, both in physiological states and during croton oil-induced intestinal inflammation. SDE (1-100 mg kg(-1)) significantly...
Several preclinical studies indicate that selective kappa-opioid receptor (KOR) antagonists have antidepressant-like effects, whereas KOR agonists have opposite effects, suggesting that each might be useful in the treatment of mood abnormalities. Salvinorin A (salvA) is a valuable KOR agonist for further study due to its high potency and receptor selectivity. However, it has short lasting...
Salvia divinorum and Mitragyna speciosa ("Kratom"), two unscheduled dietary supplements whose active agents are opioid receptor agonists, have discrete psychoactive effects that have contributed to their increasing popularity. Salvia divinorum contains the highly selective kappa- opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia. Mitragynine, the...
Ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) analysis was performed to investigate whether commercial Salvia cultivars available in the Japanese market contain salvinorin A (1), which is an hallucinogen present in magic mint (Salvia divinorum) prior to the regulation of S. divinorum by the Japanese Pharmaceutical Affairs Law. In addition, a previously reported method to...
An enantioselective synthesis of the highly functionalized trans-decalin core (2) of salvinorin A is described. The tetraene 4 was synthesized in six steps from a known L-(+)-tartaric acid derivative. Three contiguous stereocenters, two of them quaternary, on the trans-decalin were established asymmetrically by an intramolecular Diels-Alder/Tsuji allylation sequence.
ChemInformDecember 4, 2007Jonathan R. Scheerer, Jonathan F. Lawrence, Grace C. Wang et al.
Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a mu agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These...