人莫雷西嗪的代谢。I. 人尿中代谢产物的分离与鉴定。

Human moricizine metabolism. I. Isolation and identification of metabolites in human urine.

Richards L E, Pieniaszek H J, Shatzmiller S, Page G O, Blom K F, Read J M, Davidson A F, Confalone P N

DuPont Merck Pharmaceutical Co., Stine-Haskell Research Center, Newark, USA.

Xenobiotica. 1997 Feb;27(2):217-29. doi: 10.1080/004982597240703.

Abstract

Using synthetic standards and/or spectral data, seven moricizine metabolites were structurally identified in human urine. Two novel metabolites were identified as phenothiazine-2-carbamic acid and ethyl [10-(3-aminopropionyl) phenothiazin-2-yl] carbamate. Two novel human moricizine metabolites, 2-amino-10-(3-morpholino-propionyl) phenothiazine, a previously identified dog metabolite, and 2-aminophenothiazine, a previously identified rat metabolite, were also identified. Three additional human metabolites, phenothiazine-2-carbamic acid ethyl ester sulphoxide (P2CAEES), moricizine sulphoxide, and ethyl ¿10-[N-(2'-hydroxyethyl)3-aminopropionyl] phenothiazin-2-yl¿ carbamate, all previously described in the literature, were observed. 2. Both 2-amino-10-(3-morpholinopropionyl) phenothiazine and ethyl [10-(3-aminopropionyl) phenothiazin-2-yl] carbamate, and possibly ethyl ¿10-[N-(2'-hydroxyethyl) 3-aminopropionyl]phenothiazin-2-yl¿ carbamate, possess the structural characteristics thought to be necessary for class 1 antiarrhythmic activity.

摘要

利用合成标准品和/或光谱数据，在人尿中从结构上鉴定出了7种莫雷西嗪代谢物。两种新的代谢物被鉴定为吩噻嗪-2-氨基甲酸和[10-(3-氨基丙酰基)吩噻嗪-2-基]氨基甲酸乙酯。还鉴定出了两种新的人体莫雷西嗪代谢物、2-氨基-10-(3-吗啉代丙酰基)吩噻嗪（一种先前鉴定出的犬类代谢物）以及2-氨基吩噻嗪（一种先前鉴定出的大鼠代谢物）。另外还观察到三种人体代谢物，即吩噻嗪-2-氨基甲酸乙酯亚砜（P2CAEES）、莫雷西嗪亚砜以及[10-[N-(2'-羟乙基)-3-氨基丙酰基]吩噻嗪-2-基]氨基甲酸乙酯，所有这些在文献中均有过描述。2. 2-氨基-10-(3-吗啉代丙酰基)吩噻嗪和[10-(3-氨基丙酰基)吩噻嗪-2-基]氨基甲酸乙酯，以及可能的[10-[N-(2'-羟乙基)-3-氨基丙酰基]吩噻嗪-2-基]氨基甲酸乙酯，具有被认为是1类抗心律失常活性所必需的结构特征。