己巴比妥代谢：通过3'-氧代己巴比妥产生1,5-二甲基巴比妥酸和环己烯酮-谷胱甘肽加合物的新代谢途径。

Hexobarbital metabolism: a new metabolic pathway to produce 1,5-dimethylbarbituric acid and cyclohexenone-glutathione adduct via 3'-oxohexobarbital.

Takenoshita R, Nakamura T, Toki S

Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.

Xenobiotica. 1993 Aug;23(8):925-34. doi: 10.3109/00498259309059419.

Abstract

In the presence of glutathione under physiological conditions, 3'-oxohexobarbital was non-enzymically converted to 1,5-dimethylbarbituric acid and a cyclohexenone-glutathione adduct. 2. The two reaction products were characterized by mass spectrometry, 1H- and 13C-n.m.r. spectrometry, and UV spectral analyses. 3. 1,5-Dimethylbarbituric acid was excreted in urine of rat given hexobarbital, 3'-oxohexobarbital, or 1',2'-epoxyhexobarbital, and accounted for 13.4, 14.5 and 4.7% of dose, respectively. 4. The cyclohexenone-glutathione adduct, a novel metabolite of hexobarbital, was excreted in the bile of rat given hexobarbital. 5. The route of 1,5-dimethylbarbituric acid formation via 3'-oxohexobarbital in the metabolism of hexobarbital was discussed in comparison with the epoxide-diol pathway.

摘要

在生理条件下，存在谷胱甘肽时，3'-氧代己巴比妥会非酶促转化为1,5-二甲基巴比妥酸和一种环己烯酮-谷胱甘肽加合物。2. 这两种反应产物通过质谱、1H-和13C-核磁共振光谱以及紫外光谱分析进行了表征。3. 给大鼠注射己巴比妥、3'-氧代己巴比妥或1',2'-环氧己巴比妥后，1,5-二甲基巴比妥酸会随尿液排出，分别占给药剂量的13.4%、14.5%和4.7%。4. 环己烯酮-谷胱甘肽加合物是己巴比妥的一种新型代谢产物，给大鼠注射己巴比妥后会随胆汁排出。5. 与环氧化物-二醇途径相比，讨论了己巴比妥代谢过程中通过3'-氧代己巴比妥形成1,5-二甲基巴比妥酸的途径。