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

Thiruventhan Karunakaran,Kok Zhuo Ngew,Ahmad Alif Danial Zailan,Mohamad Hafizi Abu Bakar,Vivien Yi Mian Jong

doi:10.3389/fphar.2022.805986

Thiruventhan Karunakaran, Kok Zhuo Ngew + Show 3 more

Open Access

https://doi.org/10.3389/fphar.2022.805986

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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.

Highlights

Mitragynine (1) is an interesting natural product in the class of alkaloids that can be primarily isolated from the leaves of a medicinal plant, known as Mitragyna speciosa Korth (Gogineni et al, 2015)
The mitragynine (1) template and its structural information could render medicinal chemists an opportunity to develop a new analgesic that can be beneficial toward pain management and treatment
It is vital for chemists and pharmacologists to determine its maximum analgesic potency as well as alter the opioid-induced side effects through detailed preclinical and clinical studies

Summary

Introduction

Mitragynine (1) is an interesting natural product in the class of alkaloids that can be primarily isolated from the leaves of a medicinal plant, known as Mitragyna speciosa Korth (Gogineni et al, 2015). M. speciosa (Figure 1) is an indigenous and popularly cultivated plant from the Rubiaceae (coffee) family that grows in Southeast Asia, especially Malaysia and Thailand (Brown et al, 2017). In Malaysia, it is called ketum or biak-biak, while in Thailand, the plant is commonly known as kratom (Papsun et al, 2019; Chakraborty and Majumdar, 2020; Goh et al, 2021). The mitragynine (1) content in the leaves of M. speciosa varies considerably and is affected by geographical and climate conditions (Boffa et al, 2018). Takayama (2004) found that

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