N3-phenacyluridine, a novel hypnotic compound, interacts with the benzodiazepine receptor.
N3-Phenacyluridine (3-phenacyl-1-beta-D-ribofuranosyluracil) has potent sedative and hypnotic activities following intracerebroventricular injection in mice. To study the mechanism of action of N3-phenacyluridine, the interaction of this compound with the benzodiazepine receptor has been investigated. Results obtained showed that this compound inhibited specific binding of [3H]flunitrazepam to synaptic membranes of bovine cortex in a concentration-dependent fashion (IC50 = 129 microM). Scatchard analysis of [3H]flunitrazepam binding revealed that N3-phenacyluridine interacted with the ligand at the benzodiazepine receptor binding site in a competitive manner. Ro15-1788 (8-fluoro-3-carboethoxy-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a ]1, 4-benzodiazepine), a benzodiazepine receptor antagonist, also inhibited the specific binding of [3H]flunitrazepam in the presence of the compound. The results suggest that the pharmacological activity of N3-phenacyluridine may be partially mediated through the benzodiazepine receptor.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
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T
Kimura
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Kuze
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Watanabe
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Kondo
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Ho
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I
Yamamoto
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001667:Binding, Competitive; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005445:Flunitrazepam / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D011963:Receptors, GABA-A / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; C089028:N(3)-phenacyluridine; D005445:Flunitrazepam; D014529:Uridine