※ 引述《tobia (快樂就滿足)》之銘言： : 標題: Re: [問題] 美沙冬與大麻差別在哪!? : 時間: Sat Jan 2 16:29:04 2010 : Methadone的主要代謝物 : 經由N-demethylation產生 (via CYP3A4) : 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) : 是不活性的代謝物 : 參照 : Journal of Medicinal Chemistry 1973;16:909-13 : The Annals of Pharmacotherapy 2008;42:893-7 : 擁有長的半衰期、高的口服生體可用率(85%)、 : 以及不活性的代謝物等 : 是methadone作為替代療法的優點 : *但是methadone的光學異構特性與個體差異 : 使得它的半衰期變化很大 : (平均23hrs，15-60hrs，甚至可長達120hrs) : 在劑量的給予及調整上需要謹慎評估 : -- :

※ 發信站: 批踢踢實業坊(ptt.cc) : ◆ From: 220.129.161.208 : ※ 編輯: tobia 來自: 220.129.161.208 (01/02 17:02) : 推 obbear:只有經過一次N-demethylation的產物仍有活性 01/02 17:50 : → obbear:在分類上不管是嗎啡 大麻 甚至是美沙冬 都被歸為成癮類鎮痛 01/02 17:52 : → obbear:劑 不過這一大類的藥品 卻可依其結構來作次分類 我只是想說 01/02 17:53 : → obbear:美沙冬跟大麻結構以嚴格角度來看 差很多 01/02 18:14 : 推 DAHOO:不需要用嚴格的角度來看,基本上這兩個結構根本天差地遠 01/02 19:12 不好意思 我又來討論一下~~ 參照以下連結: (是free的文章) Br J Clin Pharmacol 1999;47:403-12 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014231/?tool=pubmed 這邊提到methadone經由單次demethylation之後的產物 非常不穩定 會自動環化並脫水形成EDDP (我將文字貼在最後) 不知道ob大是在那邊有找到第一次demethylation的產物仍有活性的資料呢? 以下是轉貼節錄文字: 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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