7-Hydroxymitragynine, a main active constituent of the herbal medicine Mitragyna speciosa, is an indole alkaloid that is structurally different from morphine and induced an antinociceptive effect through μ-opioid receptors. This study describes a more potent dual-acting μ- and δ-opioid agonist, MGM-16 [(E)-methyl 2-((2S,3S,7aS,12aR,12bS)-3-ethyl-9-fluoro-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12,12a,12b-decahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate], developed from 7-hydroxymitragynine for the treatment of acute and chronic pain. MGM-16 showed full agonistic effects of μ- and δ-opioid in a [35S]GTPγS binding assay and in a functional test using electrically elicited guinea pig ileum and mouse vas deferens contractions. The antinociceptive effect of MGM-16 was approximately 240 times more potent than that of morphine in a mouse tail-flick test, and its antiallodynic effect was approximately 100 times more potent than that of gabapentin in partial sciatic nerve-ligation mice. These findings suggest that MGM-16 could become a class of compounds with potential therapeutic utility for treating neuropathic pain.
See article at J Pharmacol Exp Ther 2014, 348:383–392.
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