Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.
Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.
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DOI：
10.2174/138920010794233495
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发表时间：
2010-10
影响因子：
2.3
通讯作者：
Yu AM
中科院分区：
文献类型：
--
作者：
Shen HW;Jiang XL;Winter JC;Yu AM
5-甲氧基-N，N-二甲基色胺（5-MeO-DMT）是一类天然存在的精神活性吲哚烷胺类药物。它作为一种非选择性5-羟色胺（5-HT）激动剂，引起许多生理和行为变化。5-MeO-DMT通过多态性细胞色素P450 2D 6（CYP 2D 6）O-脱甲基化为活性代谢物蟾毒替宁（bufotenine），而其主要通过单胺氧化酶A（MAO-A）介导的脱氨基途径失活。5-MeO-DMT通常与MAO-A抑制剂如Harcadine一起使用。同时使用哈洛宁可降低5-MeO-DMT脱氨基代谢，导致母体药物5-MeO-DMT以及活性代谢物蟾蜍烯碱的暴露时间延长和暴露量增加。骆驼蓬碱、5-MeO-DMT和蟾蜍烯碱对肾上腺素能系统具有激动作用，可能导致肾上腺素能过高效应或5-羟色胺毒性。有趣的是，CYP 2D 6也对肝素代谢有重要贡献，CYP 2D 6基因多态性可能导致肝素代谢、药代动力学和动力学及其与5-MeO-DMT的相互作用的相当大的变异性。本文综述了5-MeO-DMT的生物转化、药代动力学和药理作用的研究进展。此外，还讨论了harvestine和5-MeO-DMT之间的药代动力学和药效学药物-药物相互作用，CYP 2D 6药物遗传学的潜在参与以及5-MeO-DMT中毒的风险。
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as harmaline. Concurrent use of harmaline reduces 5-MeO-DMT deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-MeO-DMT, as well as the active metabolite bufotenine. Harmaline, 5-MeO-DMT and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. Interestingly, CYP2D6 also has important contribution to harmaline metabolism, and CYP2D6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-MeO-DMT. Therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT. In addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-MeO-DMT, potential involvement of CYP2D6 pharmacogenetics, and risks of 5-MeO-DMT intoxication are discussed.
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DOI：
10.1080/02791072.1979.10472093
发表时间：
1979-01-01
期刊：
JOURNAL OF PSYCHEDELIC DRUGS
影响因子：
--
作者：
CHILTON, WS;BIGWOOD, J;JENSEN, RE
通讯作者：
JENSEN, RE
DOI：
10.1081/clt-120030949
发表时间：
2004-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
Brush, DE;Bird, SB;Boyer, EW
通讯作者：
Boyer, EW
影响因子：
4.7
作者：
FULLER, RW;SNODDY, HD;PERRY, KW
通讯作者：
PERRY, KW
影响因子：
3.6
作者：
Fantegrossi, WE;Harrington, AW;Woods, JH
通讯作者：
Woods, JH
影响因子：
3.6
作者：
ABDELFATTAH, AFM;MATSUMOTO, K;WATANABE, H
通讯作者：
WATANABE, H