Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids.
Jakub Fichna, Kevin Lewellyn, Feng Yan, Bryan L. Roth, Jordan K Zjawiony
Bioorganic & Medicinal Chemistry Letters January 1, 2011 DOI: 10.1016/j.bmcl.2010.11.046 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro chemistry study Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Key points | A salvinorin A analogue substituted at C(2) with the amino acid valine (compound 12) showed high affinity and full agonist activity at the kappa-opioid receptor, while analogues with bulky or aromatic residues were inactive, which the authors attribute to the importance of size and electronegativity of C(2) substituents for binding. |
Abstract
The synthesis and in vitro evaluation of a new series of salvinorin A analogues substituted at the C(2) position with natural amino acids is reported. Compound 12, containing Val, displayed high affinity and full agonist activity at the kappa-opioid receptor. Analogues with bulky and/or aromatic residues were inactive, showing the importance of size and electronegativity of C(2)-substituents for binding affinity of salvinorin A derivatives.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 3
- Michael acceptor approach to the design of new salvinorin A-based high affinity ligands for the kappa-opioid receptor. European journal of medicinal chemistry October 6, 2014
- Solving an Old Puzzle: Elucidation and Evaluation of the Binding Mode of Salvinorin A at the Kappa Opioid Receptor Preprints.org November 1, 2022
- A Review of Salvinorin Analogs and their Kappa-Opioid Receptor Activity Bioorganic & Medicinal Chemistry Letters March 12, 2018
Cites 11
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Selective natural kappa opioid and cannabinoid receptor agonists with a potential role in the treatment of gastrointestinal dysfunction Drug News & Perspectives 2009
- CoMFA analyses of C-2 position salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity. Journal of molecular graphics & modelling April 1, 2010
- In vitrostudies on metabolism of salvinorin A Pharmaceutical Biology October 19, 2009
- 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. Journal of Pharmacology and Experimental Therapeutics March 2008
and 6 more in the library