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Kevin Tidgewell

6 papers in the library · 351 citations · publishing 2004-2007

Papers

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Synthetic studies of neoclerodane diterpenes from Salvia divinorum: exploration of the 1-position.

Bioorganic & Medicinal Chemistry Letters November 15, 2007 Kenneth G Holden, Kevin Tidgewell, Alfred Marquam et al.

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...

Salvinorin A: allosteric interactions at the mu-opioid receptor.

The Journal of pharmacology and experimental therapeutics February 1, 2007 Richard B Rothman, Daniel L Murphy, Heng Xu et al. 75 citations

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...

Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans.

The Journal of pharmacology and experimental therapeutics 2007 Eduardo R Butelman, Marek Mandau, Kevin Tidgewell et al. 64 citations

This study focused on the in vivo effects of the kappa-opioid hallucinogen salvinorin A, derived from the plant Salvia divinorum. The effects of salvinorin A (0.0032-0.056 mg/kg i.v.) were studied in a neuroendocrine biomarker assay of the anterior pituitary hormone prolactin in gonadally intact, adult male and female rhesus monkeys (n = 4 each). Salvinorin A produced dose- and time-dependent...

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 Wayne W Harding, Matthew Schmidt, Kevin Tidgewell et al. 59 citations

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...

Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates.

Synapse (New York, N.Y.) December 1, 2005 Matthew Schmidt, Mark S Schmidt, Eduardo R Butelman et al. 85 citations

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...

A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A.

Bioorganic & Medicinal Chemistry Letters October 18, 2004 Kevin Tidgewell, Wayne W Harding, Mark S Schmidt et al. 68 citations

Salvinorin A is a novel hallucinogen isolated from the widely available leaves of Salvia divinorum. Based on its mechanism of action, salvinorin A has shown potential as a stimulant abuse therapeutic. However, there are no methods for the detection of salvinorin A or its metabolites in biological fluids. In order to begin developing salvinorin A as a potential therapeutic, an understanding of...