In vivo and in vitro metabolic studies of N3-benzyluridine which exhibits hypnotic activity in mice.
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.
Kimura
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Yamamoto
I
I
Watanabe
K
K
Tateoka
Y
Y
Ho
I K
IK
D000818:Animals; D001921:Brain / Q000378:metabolism; D006207:Half-Life; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D012890:Sleep / Q000187:drug effects; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D006993:Hypnotics and Sedatives; C048028:N(3)-benzyluridine; D014529:Uridine