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在异喹胍代谢不良动物模型中,四氢异喹啉(TIQ,一种可能诱发帕金森症的物质)的代谢及脑内蓄积情况

Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer.

作者信息

Ohta S, Tachikawa O, Makino Y, Tasaki Y, Hirobe M

机构信息

Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

出版信息

Life Sci. 1990;46(8):599-605. doi: 10.1016/0024-3205(90)90128-e.

Abstract

4-Hydroxytetrahydroisoquinoline (4OH-TIQ) was detected as a metabolite of a possible parkinsonism-inducing substance, tetrahydroisoquinoline (TIQ), in rat liver microsomes and rat urine. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson's disease.

摘要

4-羟基四氢异喹啉(4OH-TIQ)在大鼠肝微粒体和大鼠尿液中被检测为一种可能诱发帕金森病的物质——四氢异喹啉(TIQ)的代谢产物。在去甲异喹胍代谢能力差的动物模型——雌性DA大鼠中,4OH-TIQ的尿排泄显著减少。雌性DA大鼠的大脑中TIQ的蓄积也显著更高。这些结果表明,在去甲异喹胍代谢能力差的个体中,代谢解毒过程受到抑制,TIQ在大脑中的蓄积增强,这可能是去甲异喹胍代谢能力差的个体易患帕金森病的一种可能解释。

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