The Chemical and Pharmacological Properties of Mitragynine and Its Diastereomers: An Insight Review

Abstract

Mitragynine, is a naturally occurring indole alkaloid that can be isolated from the leaves of a psychoactive medicinal plant. Mitragyna speciosa, also known as kratom, is found to possess promising analgesic effects on mediating the opioid receptors such as µ (MOR), δ (DOR), and κ (KOR). This alkaloid has therapeutic potential for pain management as it has limited adverse effect compared to a classical opioid, morphine. Mitragynine is frequently regarded to behave like an opioid but possesses milder withdrawal symptoms. The use of this alkaloid as the source of an analgesic candidate has been proven through comprehensive preclinical and clinical studies. The present data have shown that mitragynine is able to bind to opioid receptors, particularly MOR, to exhibit the analgesic effect. Moreover, the chemical and pharmacological aspects of mitragynine and its diastereomers, speciogynine, speciociliatine, and mitraciliatine, are discussed. It is interesting to know how the difference in stereochemical configuration could lead to the difference in the bioactivity of the respective compounds. Hence, in this review, the updated pharmacological and toxicological properties of mitragynine and its diastereomers are discussed to render a comprehensive understanding of the pharmacological properties of mitragynine and its diastereomers based on their structure–activity relationship study.

A Chromosome-Scale Genome Assembly of Mitragyna speciosa (Kratom) and the Assessment of Its Genetic Diversity in Thailand

“…However, the identity of progenitor species that underwent hybridization to give rise to M. speciosa is currently unknown. The majority of published scientific literature on M. speciosa focuses mainly on its chemical composition with mitragynine, the principal compound responsible for analgesic activity, being the most studied alkaloid from this psychoactive medicinal plant [ 7 , 8 , 9 , 10 ]. Although mitragynine possesses potent opioid agonist properties, mediating μ- and κ-opioid receptors, its chemical structure is different from those of morphine and other narcotic painkillers [ 11 ].…”

Mitragyna speciosa Korth., der Kratombaum

“…Insgesamt sind bis heute mindestens 54 Alkaloide aus der Pflanze isoliert worden, u. a. verschiedene Diastereomere des Mitragynins sowie 7-Hydroxymitragynin und eine Reihe von Oxindol-Derivaten. Neben Alkaloiden enthält die Pflanze Flavonoide, Kaffeesäurederivate, Monoterpene und Triterpenglykoside [4,5].…”

Drug testing for mitragynine and kratom: Analytical challenges and medico‐legal considerations

“… 4 , 5 The leaves may be chewed as they are, brewed into a tea, or processed as powder. However, despite therapeutic potentials in pain management, 6 possessing limited opioid adverse effects (e.g., respiratory depression) and milder withdrawal symptoms compared with morphine‐like opioids, controlled research studies are lacking, and there are no approved medical uses of kratom. 7 , 8 , 9 , 10 …”

“…4,5 The leaves may be chewed as they are, brewed into a tea, or processed as powder. However, despite therapeutic potentials in pain management, 6 possessing limited opioid adverse effects (e.g., respiratory depression) and milder withdrawal symptoms compared with morphine-like opioids, controlled research studies are lacking, and there are no approved medical uses of kratom. [7][8][9][10] Over the past decades, use of kratom as a recreational drug and self-medication herbal supplement has spread also in the Western world, 9,11 with indications of further rises during the opioid crisis and COVID-19 pandemic.…”