Evaluation of sedative-hypnotic effect of novel 4-flurobenzyloxi, 4, 6-diphenylpyrimidin-2-ol derivative

Introduction: Benzodiazepines (BZDs) are used as anxiolytic, sedative-hypnotic, muscle relaxant, and anticonvulsant agents. BZDs bind to a specific domain of the GABA-A receptor. They show lower acute toxicity in comparison to the classic ligands (e.g. barbiturates) which activate the receptor. However, BZDs may have some unwanted effects‚ including dependence and cognitive impairment. Novel derivative of 4,6-diphenylpyrimidin-2-ol, (4-(2-((4-fluorobenzyl)oxy)phenyl)-6-(4-nitrophenyl) pyrimidine-2-ol) was designed and synthesized by Department of Medical Chemistry as a ligand of benzodiazepine receptor. In this study we decided to evaluate the efficacy of the novel compound as a sedative-hypnotic agent.Methods: In this study, 32 male NMRI mice were used for pharmacological evaluation. Sedative-hypnotics effects of the novel compound, (4-(2-((4-fluorobenzyl) oxy) phenyl)-6-(4-nitrophenyl) pyrimidine-2-ol), was evaluated by open field and loss of righting reflex tests.Result: The results showed that, the novel compound at doses of 20 and 40 mg/kg significantly (p<0.001 and p<0.001 respectively) increased the sleeping time and decreased the total distance moved compared to the control group.Discussion: The novel compound, (4-(2-((4-fluorobenzyl)oxy)phenyl)-6-(4-nitrophenyl)pyrimidine-2-ol), increases the sleeping time and duration of the loss of righting reflex and decrease the locomotor activities in mice. The pharmacological effects of the compound were antagonized by flumazenil, a BZD antagonist, which confirms the involvement of BZD receptors in the biological effects Further studies are necessary to evaluate the mechanism of action and toxicity of the compound.

کلیدواژه ها:

Novel 4 ، 6-diphenylpyrimidin-2-ol derivatives ، Pentobarbital induced sleep test ، Open field test ، sedative ، hypnotic ، mice