Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.
Bioorganic & medicinal chemistry letters – May 15, 2013
Source: PubMed
Summary
Salvinorin A, nature's most potent hallucinogen, offers unique insights into brain chemistry. Scientists synthesized novel derivatives to understand how these compounds bind to specific receptors. They evaluated these new compounds' affinity for κ-, δ-, and μ-opioid receptors. Most derivatives showed strong binding to the κ-opioid receptor, with one particular compound exhibiting exceptionally high affinity. This research significantly enhances our knowledge of these crucial ligand-receptor interactions.
Abstract
Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki=2nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki=21, 36 and 39nM).