※ 引述《tobia (快乐就满足)》之铭言： : 标题: Re: [问题] 美沙冬与大麻差别在哪!? : 时间: Sat Jan 2 16:29:04 2010 : Methadone的主要代谢物 : 经由N-demethylation产生 (via CYP3A4) : 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) : 是不活性的代谢物 : 参照 : Journal of Medicinal Chemistry 1973;16:909-13 : The Annals of Pharmacotherapy 2008;42:893-7 : 拥有长的半衰期、高的口服生体可用率(85%)、 : 以及不活性的代谢物等 : 是methadone作为替代疗法的优点 : *但是methadone的光学异构特性与个体差异 : 使得它的半衰期变化很大 : (平均23hrs，15-60hrs，甚至可长达120hrs) : 在剂量的给予及调整上需要谨慎评估 : -- :

※ 发信站: 批踢踢实业坊(ptt.cc) : ◆ From: 220.129.161.208 : ※ 编辑: tobia 来自: 220.129.161.208 (01/02 17:02) : 推 obbear:只有经过一次N-demethylation的产物仍有活性 01/02 17:50 : → obbear:在分类上不管是吗啡 大麻 甚至是美沙冬 都被归为成瘾类镇痛 01/02 17:52 : → obbear:剂 不过这一大类的药品 却可依其结构来作次分类 我只是想说 01/02 17:53 : → obbear:美沙冬跟大麻结构以严格角度来看 差很多 01/02 18:14 : 推 DAHOO:不需要用严格的角度来看,基本上这两个结构根本天差地远 01/02 19:12 不好意思 我又来讨论一下~~ 参照以下连结: (是free的文章) Br J Clin Pharmacol 1999;47:403-12 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014231/?tool=pubmed 这边提到methadone经由单次demethylation之後的产物 非常不稳定 会自动环化并脱水形成EDDP (我将文字贴在最後) 不知道ob大是在那边有找到第一次demethylation的产物仍有活性的资料呢? 以下是转贴节录文字: Methadone metabolism in humans is complex, with nine metabolites identified although the data have been qualitative rather than quantitative. Mono N-demethylation, a primary metabolic pathway, results in the formation of a highly unstable compound which then undergoes spontaneous cyclization and dehydration to form 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) , which may then be further N-demethylated to 2-ethyl-5-methyl-3,3- diphenylpyrroline (EMDP) .p-hydroxylation of one aromatic ring has also been reported, resulting in the formation of four diastereomeric compounds collectively referred to as p-hydroxy methadone. After oral dosing, unchanged methadone and EDDP are found in similar amounts in the urine of humans and account for up to 50% of the dose, with only trace amounts of EMDP; other metabolites appear to contribute relatively little to the overall metabolism of methadone, although this has not been well studied, since complete mass balance has not been achieved. --

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