Central depressant activities of N3-allyluridine and N3-allylthymidine

The pharmacological effects of N3-allyluridine (N3-AUd) and N3-allylthymidine (N3-ATd) on the central nervous system (CNS) were examined by intracerebroventricular (i.c.v.) administration in mice. Pentobarbital (PB)-induced sleep, diazepam (DZ)-induced motor incoordination and spontaneous activity were used as three indices of pharmacological tests. N3-AUd and N3-ATd as well as uridine (Ud) and thymidine (Td); 0.9 mg/mouse, i.c.v., were found to potentiate PB-induced sleep, and their effects were dose dependent. Time course test showed that the most potent effects of all compounds tested on PB-induced sleep were observed at 15 min after the i.c.v. injection of these compounds. N3-AUd and N3-ATd were greater than Ud and Td in PB-induced sleep prolongation. In the DZ-induced motor incoordination experiments, N3-AUd, N3-ATd and Td exerted synergistic effect, although these compounds did not possess the motor incoordination. All compounds decreased the spontaneous activity. These results show that both N3-allylated compounds have more directly depressant effects on the CNS than the parent compounds.