Hypnotic activity of N3-benzylthymidine on mice.
The pharmacological effect in mice of N3-benzylthymidine (N3-ByTd) was examined by two routes of administration; intravenous (i.v.) and intracerebroventricular (i.c.v.), and compared with the effect of administration of N3-benzyluridine (N3-ByUd) previously reported. Hypnotic activity, pentobarbital (PB)-induced sleeping time, motor incoordination and spontaneous activity were used as indices of pharmacological effects. N3-ByTd (0.5-2.0 mumol/mouse, i.c.v.) and N3-ByUd (1.5-3.0 mumol/mouse, i.c.v.) were found to possess dose-dependent hypnotic activity, and N3-ByTd had more potent hypnotic activity than N3-ByUd. Both N3-ByTd and N3-ByUd (0.5 and 1.0 mumol/mouse, i.c.v., respectively) showed a synergistic effect on PB-induced sleep, although their parent compounds, thymidine (Td) and uridine (Ud), did not potentiate the activity at each dose. In motor incoordination, the effect of N3-ByTd (0.5 mumol/mouse) continued for 6 hr after i.c.v. injection. All compounds decreased the spontaneous activity of mice by i.c.v. administration. Furthermore, both N3-ByTd and N3-ByUd decreased the activity, when they were administered by i.v. These results reveal that both N3-benzylpyrimidine nucleosides have more direct depressant effects on the central nervous system (CNS) than the parent compounds. Among the pyrimidine nucleoside derivatives tested, N3-ByTd was found to be the most potent hypnotic substance.
Department of Hygienic Chemistry, School of Pharmacy, Hokuriku University, Kanazawa, Japan.
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Yamamoto
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Kimura
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Tateoka
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Watanabe
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Ho
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013936:Thymidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D006993:Hypnotics and Sedatives; C048028:N(3)-benzyluridine; C054535:N(3)-benzylthymidine; D010424:Pentobarbital; D013936:Thymidine; D014529:Uridine