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.