Hansson T, von Bahr C, Marklund M, Svensson J O, Ingelman-Sundberg M, Lundström J
Department of Drug Metabolism, Astra Research Centre, Södertälje, Sweden.
Pharmacol Toxicol. 1992 Dec;71(6):416-9. doi: 10.1111/j.1600-0773.1992.tb00571.x.
Incubation of the tricyclic antidepressant desmethylimpramine (DMI) with rat liver or brain microsomes in the presence of NADPH or t-butyl-hydroperoxide (TBH) revealed different regiospecificities in the hydroxylation reactions between the tissues. In brain preparations 10-OH-DMI was formed in reactions supported by NADPH or TBH, whereas in the latter case also an unidentified metabolite could be detected. Inclusion of exogenous NADPH-cytochrome P450 reductase in the brain preparations caused a 10-fold higher rate of 10-hydroxylation but no 2-OH-DMI could be detected. By contrast, liver microsomal preparations in the presence of NADPH catalyzed formation of both 2- and 10-OH-DMI, whereas only 10-OH-DMI was formed in TBH-supported reactions. The results indicate that antidepressant drugs can be metabolized in brain with different stereospecificity as compared to liver.
在存在烟酰胺腺嘌呤二核苷酸磷酸（NADPH）或叔丁基过氧化氢（TBH）的情况下，将三环类抗抑郁药去甲丙咪嗪（DMI）与大鼠肝脏或脑微粒体一起温育，结果显示不同组织在羟基化反应中具有不同的区域特异性。在脑制剂中，NADPH或TBH支持的反应中会形成10-羟基去甲丙咪嗪（10-OH-DMI），而在后一种情况下，还可检测到一种未知代谢物。在脑制剂中加入外源性NADPH-细胞色素P450还原酶，使10-羟基化速率提高了10倍，但未检测到2-羟基去甲丙咪嗪（2-OH-DMI）。相比之下，存在NADPH时，肝脏微粒体制剂催化生成2-OH-DMI和10-OH-DMI，而在TBH支持的反应中仅生成10-OH-DMI。结果表明，与肝脏相比，抗抑郁药在脑中的代谢具有不同的立体特异性。
