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.
Tateoka
Y
Y
Shinshin Chemical Industries Co., Ltd., Toyama, Japan.
Kimura
T
T
Watanabe
K
K
Yamamoto
I
I
Ho
I K
IK
D000818:Animals; D007276:Injections, Intraventricular; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013941:Thymine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology
C056086:N(1),N(3)-diallylthymine; D014498:Uracil; C056088:N(1),N(3)-diallyluracil; D006899:Mixed Function Oxygenases; D013941:Thymine; D010634:Phenobarbital