Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, United States.
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, United States; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States.
Adv Pharmacol. 2022;93:35-76. doi: 10.1016/bs.apha.2021.10.001. Epub 2021 Dec 13.
Kratom products have been historically and anecdotally used in south Asian countries for centuries to manage pain and opioid withdrawal. The use of kratom products has dramatically increased in the United States. More than 45 kratom alkaloids have been isolated, yet the overall pharmacology of the individual alkaloids is still not well characterized. The purpose of this chapter is to summarize in vitro and in vivo opioid activities of the primary kratom alkaloid mitragynine and its more potent metabolite 7-hydroxymitragynine. Following are experimental procedures described to characterize opioid receptor activity; receptor binding and functional assays, antinociceptive assays, operant conditioning assays, and respiratory plethysmography. The capacity of kratom alkaloids to confer tolerance and physical dependence as well as their pharmacokinetic properties are also summarized. The data reviewed here suggest that kratom products and mitragynine possess low efficacy agonist activity at the mu-opioid receptor in vivo. In addition, kratom products and mitragynine have been demonstrated to antagonize the effects of high efficacy mu-opioid agonists. The data further suggest that 7-hydroxymitragynine formed in vivo by metabolism of mitragynine may be minimally involved in the overall behavioral profile of mitragynine and kratom, whereas 7-hydroxymitragynine itself, at sufficiently high doses administered exogenously, shares many of the same abuse- and dependence-related behavioral effects associated with traditional opioid agonists. The apparent low efficacy of kratom products and mitragynine at mu-opioid receptors supports the development of these ligands as effective and potentially safe medications for opioid use disorder.
Kratom 产品在几个世纪以来一直被南亚国家用于治疗疼痛和缓解阿片类药物戒断症状。在美国，Kratom 产品的使用量急剧增加。目前已经分离出超过 45 种 Kratom 生物碱，但这些生物碱的整体药理学特性仍未得到很好的描述。本章的目的是总结主要 Kratom 生物碱——mitragynine 及其更有效的代谢物 7-羟基 mitragynine 的体外和体内阿片样活性。以下是描述鉴定阿片受体活性的实验程序：受体结合和功能测定、镇痛测定、操作性条件反射测定和呼吸描记术。还总结了 Kratom 生物碱产生耐受和身体依赖的能力及其药代动力学特性。本文综述的数据表明，Kratom 产品和 mitragynine 在体内对μ-阿片受体具有低效能激动剂活性。此外，已经证明 Kratom 产品和 mitragynine 可以拮抗高效μ-阿片类激动剂的作用。这些数据进一步表明，mitragynine 代谢生成的 7-羟基 mitragynine 可能很少参与 mitragynine 和 Kratom 的整体行为特征，而 7-羟基 mitragynine 本身在足够高的剂量下外源性给药时，与传统阿片类激动剂相关的滥用和依赖相关行为效应具有许多相同之处。Kratom 产品和 mitragynine 在μ-阿片受体上的低效能表明，这些配体作为治疗阿片类药物使用障碍的有效且潜在安全的药物具有发展前景。
