Metabolism of Speciociliatine, an Overlooked Kratom Alkaloid for its Potential Pharmacological Effects.
Metabolism of Speciociliatine, an Overlooked Kratom Alkaloid for its Potential Pharmacological Effects.
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DOI：
10.1208/s12248-022-00736-8
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发表时间：
2022-07-19
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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Speciociliatine, a diastereomer of mitragynine, is an indole-based alkaloid found in kratom (Mitragyna speciosa). Kratom has been widely used for the mitigation of pain and opioid dependence, as a mood enhancer, and/or as an energy booster. Speciociliatine is a partial μ-opioid agonist with a 3-fold higher binding affinity than mitragynine. Speciociliatine has been found to be a major circulating kratom alkaloid in humans following oral administration of a kratom product. In this report, we have characterized the metabolism of speciociliatine in human and preclinical species (mouse, rat, dog, and cynomolgus monkey) liver microsomes and hepatocytes. Speciociliatine metabolized rapidly in monkey, rat, and mouse hepatocytes (in vitro half-life was 6.6 ± 0.2, 8.3 ± 1.1, 11.2 ± 0.7 min, respectively), while a slower metabolism was observed in human and dog hepatocytes (91.7 ± 12.8 and >120 min, respectively). Speciociliatine underwent extensive metabolism, primarily through monooxidation and O-demethylation metabolic pathways in liver microsomes and hepatocytes across species. No human-specific or disproportionate metabolites of speciociliatine were found in human liver microsomes. The metabolism of speciociliatine was predominantly mediated by CYP3A4 with minor contributions by CYP2D6.
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DOI：
10.1016/j.jpba.2020.113778
发表时间：
2021-01-04
影响因子：
3.4
作者：
Berthold, Erin C.;Kamble, Shyam H.;McCurdy, Christopher R.
通讯作者：
McCurdy, Christopher R.
影响因子：
--
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