Salvinorin B derivatives, EOM-Sal B and MOM-Sal B, produce stimulus generalization in male Sprague-Dawley rats trained to discriminate salvinorin A.
Mary Melissa Peet, Lisa E Baker
Behavioural Pharmacology September 1, 2011 DOI: 10.1097/FBP.0b013e328349fc1b (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | Salvinorin A EOM-Sal B MOM-Sal B morphine ketamine LSD 1-(2 5-dimethoxy-4-methylphenyl)-2-aminopropane |
| Dose | 2.0 mg/kg |
| Topics | Salvia divinorum |
| Keywords | Pharmacology Drug action Potency Duration Mechanism Agents Drug discovery Novel treatments Therapeutics Medical applications Pain relief Mood disorder treatment Salvinorin a analogs Eom-sal b Mom-sal b Synthetic compounds Salvinorin a derivatives Preclinical studies Animal research Rat studies Drug testing |
| Citations | 21 |
| Key points | Both EOM-Sal B and MOM-Sal B fully substituted for salvinorin A with greater potency, and EOM-Sal B had a longer duration of action. |
Abstract
Salvinorin A, the main active component of Salvia divinorum, is a potent and selective κ opioid receptor agonist. Synthetic derivatives of this substance may be useful in the development of medicinal treatments for pain, mood disorders, and drug dependence. Such developments require extensive preclinical screening of these compounds. The drug discrimination assay is a valuable method for exploring potential similarities between novel compounds and known drugs of abuse with respect to their interoceptive stimulus properties, and can be used to investigate the potency of salvinorin A and its derivatives in vivo. This study used drug discrimination methods to compare two synthetic derivatives of salvinorin B, the ethoxymethyl ether (EOM-Sal B) and methoxymethyl ether (MOM-Sal B) with salvinorin A. Male Sprague-Dawley rats were trained to discriminate 2.0 mg/kg of salvinorin A from its vehicle (75% dimethylsulfoxide/25% water) in a fixed ratio 20 food-reinforced drug discrimination procedure, and were tested for stimulus generalization with EOM-Sal B and MOM-Sal B. For comparison, substitution tests were also conducted with a μ agonist, morphine, a dissociative hallucinogen, ketamine, and two serotonergic hallucinogens, D-lysergic diethylamide (LSD) and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane. Time-course tests were also conducted with salvinorin A and EOM-Sal B. Both EOM-Sal B and MOM-Sal B substituted fully for salvinorin A and displayed greater potency than salvinorin A. EOM-Sal B was discriminated at longer postinjection intervals than salvinorin A. Morphine and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane failed to substitute for salvinorin A, although ketamine and LSD produced significant drug-appropriate responding. The current findings are consistent with previous reports that salvinorin A produces detectable stimulus effects that are distinct from those of other drug classes and, for the first time, establish that synthetic derivatives of this substance produce similar discriminative stimulus effects. The unexpected partial substitution with LSD and ketamine indicate that further preclinical studies of these novel κ opioid receptor agonists may be warranted.
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 9
- New psychoactive substances of natural origin: A brief review Journal of Food and Drug Analysis April 18, 2017
- Ligand and G-protein selectivity in the κ-opioid receptor. Nature May 1, 2023
- Experimental strategies to discover and develop the next generation of psychedelics and entactogens as medicines Neuropharmacology December 15, 2022
- Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs. Frontiers in Psychiatry 2019
- Evaluating the abuse potential of psychedelic drugs as part of the safety pharmacology assessment for medical use in humans. Neuropharmacology November 2018
and 4 more in the library