Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.
Prabhakar R Polepally, Kate White, Eyal Vardy, Bryan L. Roth, Daneel Ferreira, Jordan K Zjawiony
Bioorganic & Medicinal Chemistry Letters May 15, 2013 DOI: 10.1016/j.bmcl.2013.03.111 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Hallucinogen Derivatives One particular compound These compounds These new compounds Opioid receptors Κ-opioid receptor Δ-opioid receptor Μ-opioid receptor Specific receptors Ligand-receptor interactions Strong binding Exceptionally high affinity Brain chemistry |
| Citations | 24 |
| Key findings | Most dicarboxylic ester derivatives of salvinorin A show high binding affinity to the κ-opioid receptor, with methyl malonyl derivative 4 having the highest affinity (Ki=2 nM). |
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).