Effects of N1,N3-diallyluracil and N1,N3-diallylthymine on hepatic drug-metabolizing enzymes of mice.

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.