Mitragynine

Mitragynine is an indole-based opioid-receptor agonist and the most abundant active alkaloid in the plant Mitragyna speciosa, commonly known as kratom and biak-biak. Dry kratom leaf contains roughly 1.2–2.1% mitragynine. Mitragynine is an indole-based opioid-receptor agonist and the most abundant active alkaloid in the plant Mitragyna speciosa, commonly known as kratom and biak-biak. Dry kratom leaf contains roughly 1.2–2.1% mitragynine. Mitragynine itself acts primarily via μ-opioid receptors, though its oxidation product mitragynine pseudoindoxyl, acts as a selective μ-opioid agonist but with less affinity for δ or κ receptors. Another alkaloid with a major contribution to the μ-opioid activity of the kratom plant is the related compound 7-hydroxymitragynine, which, while present in the plant in much smaller quantities than mitragynine, is a much more potent μ-opioid partial agonist. In murine models, the extracted alkaloids of the Kratom plant are shown to cause an insignificant amount of drug induced respiratory depression, unlike full μ-opioid agonists. Research on mitragynine structure–activity relationships have led to discovery of new potent opioid agonists, notably some C10-halogen and 2,3-ethylene glycol bridged derivatives of 7-hydroxymitragynine. The most potent one is the 10-fluoro ethylene glycol adduct of 7-hydroxymitragynine with a potency 4-fold higher than 7-hydroxymitragynine. Other modification led to 2,3-dihydro derivatives such as MGM-15, prepared by reduction of 7-hydroxymitragynine with sodium borohydride. The antinociceptive effect of MGM-15 is between 15 and 50 times more potent than that of morphine aftersubcutaneous and oral administration. Mitragynine has been studied in chronic users. It undergoes extensive hepatic metabolism with linear kinetics and long half life. Blood mitragynine concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally. Detection in body fluids is typically by liquid chromatography-mass spectrometry. It is structurally related to yohimbine but shows a totally different pharmacology. The first total synthesis of mitragynine was reported by Takayama et al. in 1995.