Kimura T, Yamamoto I, Watanabe K, Tateoka Y, Ho I K
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Res Commun Chem Pathol Pharmacol. 1991 Jan;71(1):27-48.
The metabolism of N3-benzyluridine (N3-ByUd), which possesses hypnotic activity, was studied in mice. The decrease in brain concentration of N3-ByUd was faster than that of uridine (Ud) after intracerebroventricular (i.c.v.) and intravenous (i.v.) administration. Liver and plasma concentrations of N3-ByUd were also lower than those of Ud after both i.c.v. and i.v. administrations. N3-Benzyluracil (N3-ByU) was identified as a metabolite of N3-ByUd in urine after i.c.v. administration. However, N3-ByUd was not metabolized in brain until 3 hr after i.c.v. administration. It was also not metabolized in the in vitro metabolic studies of N3-ByUd (brain and liver). The possible metabolites, e.g. Ud, uracil (U), N3-ByU and D-ribose, did not possess any hypnotic activity following i.c.v. administration. These results indicate that N3-ByUd itself, but not its metabolites, produced central nervous system (CNS) depressant activity.
对具有催眠活性的N3-苄基尿苷（N3-ByUd）在小鼠体内的代谢情况进行了研究。脑室内（i.c.v.）和静脉内（i.v.）给药后，N3-ByUd在脑中的浓度下降速度比尿苷（Ud）快。脑室内和静脉内给药后，N3-ByUd在肝脏和血浆中的浓度也低于Ud。脑室内给药后，N3-苄基尿嘧啶（N3-ByU）被鉴定为尿液中N3-ByUd的一种代谢产物。然而，脑室内给药后3小时内，N3-ByUd在脑中未发生代谢。在N3-ByUd（脑和肝脏）的体外代谢研究中，它也未发生代谢。脑室内给药后，可能的代谢产物，如Ud、尿嘧啶（U）、N3-ByU和D-核糖，均不具有任何催眠活性。这些结果表明，产生中枢神经系统（CNS）抑制活性的是N3-ByUd本身，而非其代谢产物。
