Antinociceptive Action of Mitragynine and its Synthetic Analogs in Mice

Abstract

Mitragynine is a major alkaloid extracted from the leaves of the Thai traditional herb, Mitragyna speciosa Korth (Rubiaceae). The extracts of this plant have been used as substitutes for opium and recent studies have reported that mitragynine possesses antinociceptive actions mediated via the mu opioid receptors [1]. Nonetheless, structural features of mitragynine do not fit the classical opiate ligands. Thus, the primary objectives of this study were to evaluate the antinociceptive effect of mitragynine and its synthetic analogs to determine the molecular basis of mitragynine binding to opioid receptors hence provide better understanding of the potential therapeutic roles of these compounds. The antinociceptive effect of intraperitoneal (i.p.) injection of mitragynine (10–30 mg/kg) was investigated as compared to morphine (5–10 mg/kg) using the tailflick and hotplate tests. In both tests, mitragynine exerted a dose-dependent antinociceptive activity that was maximal at 30 min but was less potent than morphine. Such effects were completely abolished by pretreatment with the opioid receptor antagonist naloxone (10 mg/kg, i.p.). The synthetic mitragynine analogs MC183, MC186, and MC187 exhibited no antinociceptive activity at 30 mg/kg dose (i.p.) in either the hotplate or tailflick tests. The present study will provide better insight into the mechanism of action of mitragynine as well as the pharmacology of opioid receptors. Such understanding may lead to the generation of a new class of analgesics of potential therapeutic value. Acknowledgements: The project described was supported by Grant Number P20RR021929 from the National Center For Research Resources.