Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy,ACS Pharmacology & Translational Science

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Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-07-31 , DOI: 10.1021/acsptsci.0c00075
Shyam H Kamble _{1,

2} , Francisco León ₃ , Tamara I King _{1,

2} , Erin C Berthold _{1,

2} , Carolina Lopera-Londoño ₃ , Kanumuri Siva Rama Raju _{1,

2} , Aidan J Hampson ₄ , Abhisheak Sharma _{1,

2} , Bonnie A Avery _{1,

2} , Lance R McMahon ₅ , Christopher R McCurdy _{2,

3}

Affiliation

Kratom is widely consumed in the United States for self-treatment of pain and opioid withdrawal symptoms. Mitragynine is the most abundant alkaloid in kratom and is a μ-opioid receptor agonist. 7-Hydroxymitragynine (7-HMG) is a mitragynine metabolite that is a more potent and efficacious opioid than its parent mitragynine. 7-HMG contributes to mitragynine’s antinociceptive effects in mice, but evidence suggests it may also have a higher abuse potential. This in vitro study demonstrates that 7-HMG is stable in rodent and monkey plasma but is unstable in human plasma. Surprisingly, in human plasma 7-HMG is converted to mitragynine pseudoindoxyl, an opioid that is even more potent than either mitragynine or 7-HMG. This novel metabolite is formed in human plasma to a much greater extent than in the preclinical species tested (mouse, rat, dog, and cynomolgus monkey) and due to its μ-opioid potency may substantially contribute to the pharmacology of kratom in humans to a greater extent than in other tested species.

中文翻译：

Kratom 生物碱代谢物在人体血浆中的代谢增加了其阿片类药物的效力和功效

Kratom 在美国被广泛用于自我治疗疼痛和阿片类药物戒断症状。Mitragynine 是 kratom 中含量最丰富的生物碱，是一种 μ-阿片受体激动剂。7-Hydroxymitragynine (7-HMG) 是一种 mitragynine 代谢物，是一种比其母体 mitragynine 更有效和更有效的阿片类药物。7-HMG 有助于米特拉吉宁对小鼠的镇痛作用，但有证据表明它也可能具有更高的滥用潜力。这种体外研究表明 7-HMG 在啮齿动物和猴血浆中稳定，但在人血浆中不稳定。令人惊讶的是，在人血浆中，7-HMG 被转化为帽柱木碱假吲哚酚，这是一种比帽柱木碱或 7-HMG 更有效的阿片类药物。这种新的代谢物在人血浆中的形成程度比在测试的临床前物种（小鼠、大鼠、狗和食蟹猴）中形成的程度要大得多，并且由于其 μ-阿片类药物的效力，可能对 kratom 在人体中的药理学作用产生重大影响程度高于其他测试物种。

更新日期：2020-07-31

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