Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna speciosa

Abstract

The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.

Determination of mitragynine in rat plasma by LC–MS/MS: Application to pharmacokinetics

“…H NMR spectra of purified MIT were analyzed according to characterization data published previously [9]. The structure of the compound was also confirmed by X-ray analysis (data not shown).…”

Metabolism studies of the Kratom alkaloids mitraciliatine and isopaynantheine, diastereomers of the main alkaloids mitragynine and paynantheine, in rat and human urine using liquid chromatography–linear ion trap-mass spectrometry

“…(Thai name Kratom; Rubiaceae) is a medical plant native to Thailand and other Southeast Asian countries [1,2]. Various alkaloids in varying concentrations could be identified in several plant species and/or plant parts [3][4][5]. For example, M. speciosa leaves from adult plants in Thailand have been reported to contain as main alkaloid approximately over 60% mitragynine (MG), those from Malaysia only over 10%.…”

“…Maurer). [5]. Shellard et al [4] described the distribution and probable biogenetic route of M. speciosa in young and mature leaves from Thailand.…”

The cellular toxicology of mitragynine, the dominant alkaloid of the narcotic-like herb, Mitragyna speciosa Korth

“…This characteristic of the plant has led to it being highly abused by drug addicts 4 . The chemistry and pharmacology of the leaves of this plant, especially the dominant alkaloid, mitragynine (MIT, Figure 1), is known to include opioid-like agonistic effects 1, 5,6 . MIT was reported to exert antinociceptive and anti-tussive effects upon oral, subcutaneous and intraperitoneal administration to rodents 7 .…”