Salvinorin B methoxymethyl ether (2-O-methoxymethylsalvinorin B) is a semi-synthetic analogue of the natural product salvinorin A used in scientific research.[1][2] It has a longer duration of action of around 2–3 hours, compared to less than 30 minutes for salvinorin A,[3] and has increased affinity and potency at the κ-opioid receptor. It is prepared from salvinorin B.[4] The crystal structure is almost superimposable with that of salvinorin A.[5] Structures bound to the κ-opioid receptor have also been reported.[6]
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| Formula | C23H30O8 |
| Molar mass | 434.485 g·mol−1 |
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Salvinorin B methoxymethyl ether has a Ki of 0.60 nM at the κ opioid receptor,[7] and is around five times more potent than salvinorin A in animal studies, although it is still only half as potent as its ethoxymethyl ether homolog, 'symmetry'.[7][8][9]
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editReferences
edit- ^ Inan S, Lee DY, Liu-Chen LY, Cowan A (March 2009). "Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A". Naunyn-Schmiedeberg's Archives of Pharmacology. 379 (3): 263–270. doi:10.1007/s00210-008-0358-8. PMID 18925386. S2CID 8123431.
- ^ McLennan GP, Kiss A, Miyatake M, Belcheva MM, Chambers KT, Pozek JJ, et al. (December 2008). "Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways". Journal of Neurochemistry. 107 (6): 1753–1765. doi:10.1111/j.1471-4159.2008.05745.x. PMC 2606093. PMID 19014370.
- ^ Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, et al. (March 2008). "2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A". The Journal of Pharmacology and Experimental Therapeutics. 324 (3): 1073–1083. doi:10.1124/jpet.107.132142. PMC 2519046. PMID 18089845.
- ^ Lee DY, Karnati VV, He M, Liu-Chen LY, Kondaveti L, Ma Z, et al. (August 2005). "Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues". Bioorganic & Medicinal Chemistry Letters. 15 (16): 3744–3747. doi:10.1016/j.bmcl.2005.05.048. PMID 15993589.
- ^ Munro TA, Ho DM, Cohen BM (2012). "Salvinorin B methoxymethyl ether". Acta Crystallographica Section E. 68 (11): o3225–o3226. Bibcode:2012AcCrE..68o3225M. doi:10.1107/s1600536812043449. PMC 3515309. PMID 23284529.
- ^ Han J, Zhang J, Nazarova AL, Bernhard SM, Krumm BE, Zhao L, et al. (May 2023). "Ligand and G-protein selectivity in the κ-opioid receptor". Nature. 617 (7960): 417–425. Bibcode:2023Natur.617..417H. doi:10.1038/s41586-023-06030-7. PMC 10172140. PMID 37138078.
- ^ a b Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, et al. (February 2008). "Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers". Bioorganic & Medicinal Chemistry. 16 (3): 1279–1286. doi:10.1016/j.bmc.2007.10.067. PMC 2568987. PMID 17981041.
- ^ Baker LE, Panos JJ, Killinger BA, Peet MM, Bell LM, Haliw LA, Walker SL (April 2009). "Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats". Psychopharmacology. 203 (2): 203–211. doi:10.1007/s00213-008-1458-3. PMID 19153716.
- ^ Mercury D, Feelodd D (2008). "First look at a new psychoactive drug: symmetry (salvinorin B ethoxymethyl ether)". Entheogen Review. 16 (4): 136–145. ISSN 1066-1913.