Tateoka Y, Kimura T, Watanabe K, Yamamoto I, Ho I K
Shinshin Chemical Industries Co., Ltd., Toyama, Japan.
Res Commun Chem Pathol Pharmacol. 1989 Apr;64(1):135-43.
Potentiation mechanism of pentobarbital (PB)-induced sleep by N1,N3-diallyluracil (DAU) and N1,N3-diallylthymine (DAT) was studied in mice. In mice receiving DAU (40 mg/kg, i.p.) 180 min earlier, PB (40 mg/kg, i.p.)-induced sleeping time was significantly enhanced. At this time point, DAU administration also significantly decreased the enzyme activity of ethylmorphine (EM) N-demethylase and the content of cytochrome P-450 in the mouse hepatic microsomes. On the other hand, DAT (40 mg/kg, i.p.) showed significance prolonging effect until 60 min after administration. DAT significantly decreased the content of cytochrome P-450 at 10, 60 and 180 min. DAU exhibited non-competitive inhibition on the EM N-demethylase activity in vitro and DAT showed inhibition of mixed type. However, only DAU (200 micrograms/mouse) significantly prolonged the PB (40 mg/kg, i.p.)-induced sleeping time by intracerebroventricular (i.c.v.) routes of administration. These results suggest that DAU prolonged PB-induced sleep by both the CNS depressant effect and the inhibition of the PB metabolism, whereas DAT enhanced sleep is partly responsible only or its inhibition of PB metabolism.
在小鼠中研究了N1,N3 - 二烯丙基尿嘧啶（DAU）和N1,N3 - 二烯丙基胸腺嘧啶（DAT）对戊巴比妥（PB）诱导睡眠的增强机制。在提前180分钟腹腔注射DAU（40mg/kg）的小鼠中，腹腔注射PB（40mg/kg）诱导的睡眠时间显著延长。此时，给予DAU还显著降低了小鼠肝微粒体中乙基吗啡（EM）N - 脱甲基酶的酶活性和细胞色素P - 450的含量。另一方面，DAT（40mg/kg，腹腔注射）在给药后60分钟内显示出显著的延长作用。DAT在10、60和180分钟时显著降低细胞色素P - 450的含量。DAU在体外对EM N - 脱甲基酶活性表现出非竞争性抑制，而DAT表现出混合型抑制。然而，只有DAU（200微克/小鼠）通过脑室内（i.c.v.）给药途径显著延长了腹腔注射PB（40mg/kg）诱导的睡眠时间。这些结果表明，DAU通过中枢神经系统抑制作用和对PB代谢的抑制来延长PB诱导的睡眠，而DAT增强睡眠仅部分归因于其对PB代谢的抑制。
