Synapse (New York, N.Y.)
December 1, 2005
Matthew D Schmidt, Mark S Schmidt, Eduardo R Butelman et al.
85 citations
Salvinorin A, a potent hallucinogen from Salvia divinorum, is rapidly eliminated from the body after intravenous administration in rhesus monkeys, with an average elimination half-life of about 57 minutes. Pharmacokinetic differences in distribution half-life, elimination half-life, and area under the curve were observed between males and females, suggesting potential sex differences in the drug's effects. The presumed major metabolite, salvinorin B, was not detected in the study, though it is known to accumulate outside the body.
The Journal of pharmacology and experimental therapeutics
February 1, 2007
Richard B Rothman, Daniel L Murphy, Heng Xu et al.
75 citations
Salvinorin A, a hallucinogenic compound that activates kappa-opioid receptors, also partially inhibits mu-opioid receptor binding through an allosteric mechanism. In cells expressing human mu-opioid receptors, salvinorin A reduced binding of two different radioligands (DAMGO and diprenorphine) in a dose-dependent, nonlinear way, altering both the number of binding sites and their affinity. It also slowed the dissociation of these ligands from the receptor and acted as an uncompetitive inhibitor of receptor signaling. Similar effects were observed in rat brain tissue. Together, these findings indicate that salvinorin A modulates the mu-opioid receptor allosterically, not by binding at the same site as typical opioids.
Bioorganic & medicinal chemistry letters
October 18, 2004
Kevin Tidgewell, Wayne W Harding, Mark Schmidt et al.
68 citations
Salvinorin A, a hallucinogen from Salvia divinorum, may serve as a therapeutic for stimulant abuse, but no methods exist to detect it or its metabolites in biological fluids. This work describes a straightforward synthesis of a deuterium-labeled analog of salvinorin A and its use as an internal standard for detecting salvinorin A and its metabolites in biological fluids using LC-MS, providing a tool for studying its metabolism and potential therapeutic development.
The Journal of pharmacology and experimental therapeutics
January 1, 2007
Eduardo R Butelman, Marek Mandau, Kevin Tidgewell et al.
64 citations
The hallucinogen salvinorin A, derived from the plant Salvia divinorum, acts as a high-efficacy kappa-opioid agonist in nonhuman primates. In a neuroendocrine biomarker assay measuring the anterior pituitary hormone prolactin, salvinorin A produced dose- and time-dependent effects in adult male and female rhesus monkeys (n = 4 each). It was approximately equipotent to the synthetic kappa-agonist U69,593 (ED50 0.015 mg/kg vs. 0.0098 mg/kg) but had a shorter duration. The effects were blocked by a high dose of the opioid antagonist nalmefene (0.1 mg/kg) but not by a low dose (0.01 mg/kg) or by the 5HT2 receptor antagonist ketanserin. Effects were more robust in females. Cloning of the rhesus monkey kappa-opioid receptor gene showed high homology with the human gene.
Journal of natural products
January 1, 2006
Wayne W Harding, Matthew Schmidt, Kevin Tidgewell et al.
59 citations
Salvinorin A, a hallucinogen from the plant Salvia divinorum, is unique as the first non-nitrogenous compound known to bind to opioid receptors. To understand why it selectively targets kappa opioid receptors, researchers systematically altered its structure and tested the effects on receptor binding and activity. This work describes chemical transformations of salvinorin A, including a semisynthesis of salvinicins A and B. It also identifies compound 10a as the first neoclerodane diterpene with delta opioid antagonist activity, providing new tools for studying opioid receptor interactions.