22-azidosalvinorin A exhibits antidepressant-like effect in mice.
James Oluwagbamigbe Fajemiroye, Polepally Reddy Prabhakar, Luiz Carlos da Cunha, Elson Alves Costa, Jordan K Zjawiony
European Journal of Pharmacology April 5, 2017 DOI: 10.1016/j.ejphar.2017.02.031 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | 22-azidosalvinorin A (SA2) |
| Dose | 5, 10 and 20 mg/kg |
| Topics | Depression Salvia divinorum |
| Keywords | 22-azidosalvinorin a Adrenoceptors Monoamines Κ-opioid receptor |
| Key points | SA2 induced monoamine-mediated antidepressant-like effect in mice, as shown by decreased immobility in behavioral tests. |
Abstract
The increasing cases of depression has made the searches for new drugs and understanding of the underligning neurobiology of this psychiatric disorder a necessity. Here, we modified the structure of salvinorin A (a known halucinogen) and investigated antidepressant-like activity of its four derivatives; 22-methylsulfanylsalvinorin A(SA1), 2-O-cinnamoylsalvinorin B (CSB), 22-azidosalvinorin A (SA2), and 2-O-(4'-azidophenylsulfonyl)salvinorin B (SA3). Prior to behavioural tests (Irwin test, open field test - OFT, forced swimming test - FST and tail suspension test - TST), SA1 was prepared by reacting salvinorin B and methylthioacetic acid with 89% yield; CSB was obtained from the reaction of salvinorin B and cinnamic acid with 92% yield; SA2 was obtained from the reaction of salvinorin B and azidoacetic acid with 81% yield; and SA3 was prepared by reacting salvinorin B with 4-azidophenylsulfonyl chloride with 80% yield. Oral treatment of mice with these derivatives (1-1000mg/kg) did not elicit toxic sign or death. Unlike SA, SA1, CSB and SA3, treatment with SA2 (5, 10 and 20mg/kg) decreased the immobility (TST and FST) and swimming time (FST) without altering locomotor activity in OFT. A decrease in the immobility time in TST and FST confirmed antidepressant-like property of SA2. Although p-chlorophenylalanine (serotonin depletor) or WAY100635 (selective 5-HT1A receptor antagonist) did not attenuate effect of SA2, alpha-methyl-para-tyrosine (catecholamine depletor) and prazosin (selective α1-receptor antagonist) attenuated this effect. SA2 mildly inhibited monoamine oxidase and showed affinity for α1A, α1B, α1D and κ-opioid receptor subtypes. In summary, SA2 induced monoamine-mediated antidepressant-like effect.
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 4
- Total Synthesis of the Neoclerodane Diterpene Salvinorin A via an Intramolecular Diels–Alder Strategy Organic Letters May 22, 2018
- The translational potential of salvinorin A: systematic review and meta-analysis of preclinical studies. Translational Psychiatry October 10, 2025
- A Protecting-Group-Free Synthesis of (-)-Salvinorin A. Chemistry - A European Journal May 20, 2021
- Salvindolin elicits opioid system-mediated antinociceptive and antidepressant-like activities. Journal of Psychopharmacology July 2019
Cites 21
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Modification of 5‐HT neuron properties by sustained administration of the 5‐HT1A agonist gepirone: Electrophysiological studies in the rat brain Synapse 1987
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). Journal of Ethnopharmacology May 1, 1983
- Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology March 1, 2013
and 16 more in the library