大鼠体内与体外H1拮抗剂N,N-二甲基-N'-2-吡啶基-N'-(2-噻吩基甲基)-1,2-乙二胺（美沙吡啉）代谢产物的比较

A comparison of in vivo and in vitro metabolites of the H1-antagonist N,N-dimethyl-N'-2-pyridyl-N'-(2-thienylmethyl)-1,2-ethanediamine (methapyrilene) in the rat.

Singer S S, Lijinsky W, Kratz L E, Castagnoli N, Rose J E

NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701.

Xenobiotica. 1987 Nov;17(11):1279-91. doi: 10.3109/00498258709047159.

Abstract

The H1-antagonist N,N-dimethyl-N'-2-pyridyl-N'-(2-thienylmethyl)-1,2-ethanediamine (methapyrilene) is carcinogenic in rats. 2. The compound, which is inactive in short-term tests and does not bind to DNA, has been classified as a non-genotoxic carcinogen. 3. Studies have been made in vitro and in vivo in F344 and Sprague-Dawley rats. New metabolites included N-(N',N'-dimethylaminoethyl)-2-aminopyridine and the corresponding N'-oxide, a derivative in which methapyrilene is hydroxylated on the 5-position of the pyridine ring, 2-(N',N'-dimethylamino)-N-2'-pyridylacetamide, N-(2-pyridyl)-N-2"-thienylmethyl)aminoacetaldehyde, and 2-hydroxymethylthiophene. 4. Both strains of rat metabolize methapyrilene to reactive species which may be of importance in the carcinogenic process.

摘要

H1拮抗剂N,N-二甲基-N'-2-吡啶基-N'-(2-噻吩基甲基)-1,2-乙二胺（美吡拉敏）对大鼠具有致癌性。2. 该化合物在短期试验中无活性且不与DNA结合，已被归类为非遗传毒性致癌物。3. 已在F344和Sprague-Dawley大鼠中进行了体外和体内研究。新的代谢产物包括N-(N',N'-二甲基氨基乙基)-2-氨基吡啶及其相应的N'-氧化物，一种美吡拉敏在吡啶环5位羟基化的衍生物，2-(N',N'-二甲基氨基)-N-2'-吡啶基乙酰胺，N-(2-吡啶基)-N-2"-噻吩基甲基)氨基乙醛，以及2-羟甲基噻吩。4. 两种品系的大鼠都将美吡拉敏代谢为可能在致癌过程中起重要作用的活性物质。