Karunakaran Thiruventhan, Ngew Kok Zhuo, Zailan Ahmad Alif Danial, Mian Jong Vivien Yi, Abu Bakar Mohamad Hafizi
Centre for Drug Research, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
School of Chemical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
Front Pharmacol. 2022 Feb 24;13:805986. doi: 10.3389/fphar.2022.805986. eCollection 2022.
Mitragynine, is a naturally occurring indole alkaloid that can be isolated from the leaves of a psychoactive medicinal plant. , also known as kratom, is found to possess promising analgesic effects on mediating the opioid receptors such as (MOR), (DOR), and (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.
帽柱木碱是一种天然存在的吲哚生物碱,可从一种具有精神活性的药用植物的叶子中分离出来。这种植物也被称为 kratom,已发现其对介导 μ 阿片受体(MOR)、δ 阿片受体(DOR)和 κ 阿片受体(KOR)等阿片受体具有显著的镇痛作用。与传统阿片类药物吗啡相比,这种生物碱的副作用有限,因此在疼痛管理方面具有治疗潜力。帽柱木碱常被认为具有类似阿片类药物的作用,但戒断症状较轻。通过全面的临床前和临床研究,已证明将这种生物碱用作镇痛候选药物的来源是可行的。目前的数据表明,帽柱木碱能够与阿片受体结合,特别是 MOR,以发挥镇痛作用。此外,还讨论了帽柱木碱及其非对映异构体异帽柱木碱、异帽柱碱和帽柱碱的化学和药理学方面。了解立体化学构型的差异如何导致各化合物生物活性的差异是很有趣的。因此,在本综述中,讨论了帽柱木碱及其非对映异构体的最新药理学和毒理学特性,以便基于其构效关系研究全面了解帽柱木碱及其非对映异构体的药理学特性。