Kimura T, Kuze J, Watanabe K, Kondo S, Ho I K, Yamamoto I
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Eur J Pharmacol. 1996 Sep 12;311(2-3):265-9. doi: 10.1016/0014-2999(96)00434-7.
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.
N3-苯甲酰甲基尿苷（3-苯甲酰甲基-1-β-D-呋喃核糖基尿嘧啶）经小鼠脑室内注射后具有强效的镇静和催眠活性。为研究N3-苯甲酰甲基尿苷的作用机制，已对该化合物与苯二氮䓬受体的相互作用进行了研究。所得结果表明，该化合物以浓度依赖性方式抑制[3H]氟硝西泮与牛脑皮质突触膜的特异性结合（IC50 = 129 microM）。对[3H]氟硝西泮结合的Scatchard分析表明，N3-苯甲酰甲基尿苷以竞争性方式与苯二氮䓬受体结合位点处的配体相互作用。苯二氮䓬受体拮抗剂Ro15-1788（8-氟-3-乙氧羰基-5,6-二氢-5-甲基-6-氧代-4H-咪唑并[1,5a][1,4]苯并二氮杂䓬）在该化合物存在的情况下也抑制了[3H]氟硝西泮的特异性结合。结果表明，N3-苯甲酰甲基尿苷的药理活性可能部分通过苯二氮䓬受体介导。
