2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A.
Yulin Wang, Yong Chen, Wei Xu, David Y W Lee, Zhongze Ma, Scott M. Rawls, Alan Cowan, Lee-Yuan Liu-Chen
Journal of Pharmacology and Experimental Therapeutics March 2008 DOI: 10.1124/jpet.107.132142 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical pharmacology study Peer reviewed |
|---|---|
| Population | Chinese hamster ovary cells stably expressing KOPR, mice, and rats |
| Interventions | MOM-Sal B U50 488H salvinorin A norbinaltorphimine |
| Dose | MOM-Sal B 0.05-1 mg/kg s.c.; MOM-Sal B 1-5 mg/kg s.c.; MOM-Sal B 0.5-5 mg/kg i.p.; salvinorin A 10 mg/kg |
| Measures | guanosine 5'-O-(3-[(35)S]thio)triphosphate binding, hot-plate test, Y-maze ambulation, immobility, hypothermia |
| Topics | Salvia divinorum |
| Key points | MOM-Sal B is a potent, selective full agonist at the kappa opioid receptor, with approximately 3-fold higher binding affinity and approximately 5- to 7-fold greater potency than U50,488H and salvinorin A. In rodents it produced KOPR-mediated immobility, increased Y-maze ambulation, antinociception, and hypothermia, with longer-lasting in vivo effects than salvinorin A. |
Abstract
Salvinorin (Sal) A is a naturally occurring, selective kappa opioid receptor (KOPR) agonist with a short duration of action in vivo. Pharmacological properties of a C(2) derivative, 2-methoxymethyl (MOM)-Sal B, were characterized. MOM-Sal B bound to KOPR with high selectivity and displayed approximately 3-fold higher affinity than U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate] and Sal A. It acted as a full agonist at KOPR in guanosine 5'-O-(3-[(35)S]thio)triphosphate binding and was approximately 5- and approximately 7-fold more potent than U50,488H and Sal A, respectively. In Chinese hamster ovary cells stably expressing KOPR, all three kappa agonists internalized or down-regulated KOPR to similar extents, with MOM-Sal B being the most potent. In mice, MOM-Sal B (0.05-1 mg/kg s.c.) caused immediate and dose-dependent immobility lasting approximately 3 h, which was blocked by norbinaltorphimine. In contrast, ambulation in a Y-maze was increased when rats received MOM-Sal B (1-5 mg/kg s.c.). In addition, MOM-Sal B (0.5-5 mg/kg i.p.) produced antinociception (hot-plate test) and hypothermia in a dose-dependent manner in rats. MOM-Sal B was more potent than U50,488H in both tests and more efficacious than U50,488H in the hot-plate test. These latter two in vivo effects were blocked by norbinaltorphimine, indicating KOPR-mediated actions. Sal A at 10 mg/kg elicited neither antinociception nor hypothermia 30 min after administration to rats. In summary, MOM-Sal B is a potent and efficacious KOPR agonist with longer lasting in vivo effects than Sal A.
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 30
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Ligand and G-protein selectivity in the κ-opioid receptor. Nature May 1, 2023
- Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders Frontiers in Pharmacology September 8, 2015
- Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats. Psychopharmacology April 1, 2009
- Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A. MedChemComm December 1, 2011
and 25 more in the library
Cites 16
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- 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
- 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. Psychopharmacology May 1, 2005
- Salvia divinorum and the unique diterpene hallucinogen, Salvinorin (divinorin) A. Journal of Psychoactive Drugs 1994
- Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice. Journal of Pharmacology and Experimental Therapeutics August 1, 2006
and 11 more in the library