Coutts R T, Hussain M S, Baker G B
Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
J Psychiatry Neurosci. 1991 Dec;16(5):272-5.
Major metabolites of trimipramine in young male Sprague-Dawley rats are the result of alicyclic and aromatic ring oxidation. The four major urinary metabolites have been identified as 10-oxotrimipramine, 2-hydroxytrimipramine, 2-hydroxynortrimipramine, and 2-hydroxy-10-oxotrimipramine. When iprindole was administered to rats prior to trimipramine, the effect on trimipramine metabolism was profound. The formation of both 10-oxo metabolites was virtually completely inhibited; the production of 2-hydroxytrimipramine was significantly reduced while the metabolic formation of 2-hydroxynortrimipramine was increased. It is apparent from these preliminary results that metabolic alicyclic and aromatic hydroxylations are catalyzed by different cytochrome P450 isozymes and more than one P450 isozyme is involved in the aromatic ring oxidation of trimipramine and nortrimipramine.
在年轻雄性斯普拉格-道利大鼠体内，三甲丙咪嗪的主要代谢产物是脂环族和芳香环氧化的结果。已鉴定出四种主要的尿液代谢产物为10-氧代三甲丙咪嗪、2-羟基三甲丙咪嗪、2-羟基去甲丙咪嗪和2-羟基-10-氧代三甲丙咪嗪。当在给予三甲丙咪嗪之前给大鼠施用茚满二酮时，对三甲丙咪嗪代谢的影响是显著的。两种10-氧代代谢产物的形成几乎完全受到抑制；2-羟基三甲丙咪嗪的生成显著减少，而2-羟基去甲丙咪嗪的代谢生成增加。从这些初步结果可以明显看出，脂环族和芳香族羟基化代谢是由不同的细胞色素P450同工酶催化的，并且不止一种P450同工酶参与了三甲丙咪嗪和去甲丙咪嗪的芳香环氧化。
