大鼠体内[3H]-(+)-8-氯-5-(2,3-二氢苯并呋喃-7-基)-7-甲氧基甲氧基-3-甲基-2,3,4,5-四氢-1H-3-苯并氮杂䓬主要代谢产物的鉴定

Identification of the major metabolites of [3H]-(+)-8-chloro-5-(2,3- dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrahydro- 1H-3- benzazepine in rats.

Nordholm L, Wassmann O, Nielsen P G, Thøgersen H, Grønvald F

Department of Drug Metabolism, Novo Nordisk CNS Division, Måløv, Denmark.

Xenobiotica. 1992 Mar;22(3):345-56. doi: 10.3109/00498259209046646.

Abstract

The in vivo urinary metabolites of 3H(+)-8-chloro-5(2,3- dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrah ydro-1H-3- benzazepine isolated from Wistar rats have been characterized by mass spectrometry and n.m.r. spectroscopy. 2. Metabolites are formed by N-demethylation, hydroxylation of the dihydrobenzofuran moiety, and elimination of the methoxymethyl group followed by glucuronidation. All combinations of these metabolic pathways were found in the metabolites in urine. 3. In the faeces metabolites formed by hydroxylation of the dihydrobenzofuran moiety and elimination of the methoxymethyl moiety dominate, while N-demethylated metabolites are present only in small amounts. 4. The major plasma metabolite was formed by elimination of the methoxymethyl group followed by glucuronidation. Only minute amounts of other metabolites were present.

摘要

从Wistar大鼠体内分离出的3H(+)-8-氯-5(2,3-二氢苯并呋喃-7-基)-7-甲氧基甲氧基-3-甲基-2,3,4,5-四氢-1H-3-苯并氮杂䓬的体内尿液代谢产物已通过质谱和核磁共振光谱进行了表征。2. 代谢产物通过N-去甲基化、二氢苯并呋喃部分的羟基化以及甲氧基甲基的消除，随后进行葡萄糖醛酸化形成。在尿液中的代谢产物中发现了这些代谢途径的所有组合。3. 在粪便中，由二氢苯并呋喃部分的羟基化和甲氧基甲基部分的消除形成的代谢产物占主导，而N-去甲基化代谢产物仅少量存在。4. 主要的血浆代谢产物是由甲氧基甲基的消除，随后进行葡萄糖醛酸化形成的。仅存在极少量的其他代谢产物。