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.
Bioorganic & medicinal chemistry letters
June 1, 2013
Warunya Arunotayanun, Jeffrey W Dalley, Xi-Ping Huang et al.
41 citations
Two widely marketed novel psychoactive drugs, alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine, were analyzed for their chemical structure and binding to serotonin receptor subtypes. These tryptamine-derived compounds, sold without restriction, can cause psychosis and hallucinations that may lead to injury or death. The study elucidates their structures and receptor binding profiles, providing insight into their pharmacological actions.
Bioorganic & medicinal chemistry letters
February 1, 2016
Nicholas V. Cozzi, Paul F. Daley
24 citations
N,N-Diallyltryptamine (DALT) and its 5-methoxy derivative (5-MeO-DALT) are tryptamines originally synthesized by Alexander Shulgin, with 5-MeO-DALT reported psychoactive at 12-20 mg and DALT showing few effects at 42-80 mg. This study synthesized additional 5-substituted-DALTs and measured their binding affinities at 45 cloned receptors and transporters. Five DALT compounds had affinities of 10-80 nM for serotonin 5-HT1A and 5-HT2B receptors, while DALT itself had 100 nM affinity at 5-HT1A. Affinities at 5-HT2A receptors were weakest (250-730 nM). Five compounds showed 50-400 nM affinity for 5-HT1D, 5-HT6, and 5-HT7 receptors. Binding also occurred at adrenergic, sigma, histamine, and transporter sites. Quantitative structure-affinity relationships revealed correlations with steric, electronic, and hydrophobic parameters, aiding future drug development.
Bioorganic & medicinal chemistry letters
May 15, 2013
Prabhakar R Polepally, Kate White, Eyal Vardy et al.
24 citations
Salvinorin A, the active ingredient in the hallucinogenic plant Salvia divinorum, is nature's most potent hallucinogen and selectively activates the κ-opioid receptor. To explore how these compounds bind to specific receptors, researchers synthesized a series of dicarboxylic ester derivatives of salvinorin A and tested their binding affinity at κ-, δ-, and μ-opioid receptors. Most of the new compounds showed high affinity for the κ-opioid receptor. The methyl malonyl derivative 4 had the strongest binding, with a Ki of 2 nM, while analogues 5, 7, and 14 also exhibited significant affinity, with Ki values of 21, 36, and 39 nM respectively. These findings provide insights into brain chemistry and ligand-receptor interactions.