豆腐果苷衍生物W0620实验性抗抑郁作用量效关系研究

目的: 观察豆腐果苷衍生物W0620 对悬尾小鼠不动时间的影响并初步探讨其剂量与效应关系。方法: 应用行为绝望抑郁模型———小鼠悬尾实验研究不同剂量W0620 对实验小鼠不动时间的影响, 同时应用小鼠自主活动实验观察不同剂量W0620 对中枢兴奋作用的影响。结果: 5.91 、17.73 、53.20 、159.60 mg /kg 4 个剂量组对小鼠自主活动均无影响(P >0.05), 17.73 、53.20 、159.60 mg /kg 3 个剂量组能明显缩短悬尾实验中小鼠的不动时间(P <0.01) 。W0620 的对数剂量与抗抑郁药效呈现S 型量效关系, 药效动力学参数如下:Emax 80.79 s 、E_base 12.13 s 、K 9.16 mg /kg 、H 3.38 、ED₅₀ 9.16 mg /kg 、E₅₀ 46.46 s 、ED₈₀ 13.81 mg /kg 、E₈₀ 67.05 s 、ED₉₀ 17.56 mg /kg 、E₉₀ 73.92 s 。结论: W0620 有明显抗抑郁作用, 其量效关系符合S 型曲线, 无明显中枢抑制作用。

Experimental study for antidepressant effects on the dose-effect relationship of Helicid derivate W0620

AIM: To investigate the dose-effect relationship of Helicid derivate W0620 for immobility time using the tail suspension test in mice. METHODS: Antidepressant effects of different dosage of W0620 were studied on the behavioral despair animal model-tail suspension test in mice, and the stimulative effects on the central nervous system (CNS) were observed by the autonomic activity test in mice. RESULTS: Four dose groups of W0620(5.91, 17.73, 53.20, 159.60 mg /kg) had no effects on autonomic activity in mice (P >0.05), and three dose groups of W0620(17.73, 53.20, 159.60 mg /kg) could significantly shorten the mice immobility time (P <0.01) compared with that of the control group. A sigmoid curvilinear relationship was shown between the logarithmic doses of W0620 and the antidepressant effects, the pharmacodynamic parameters were as follow: E_max 80.79 s, E_base 12.13 s, K 9.16 mg /kg, H 3.38, ED₅₀ 9.16 mg /kg, E₅₀ 46.46 s, ED₈₀ 13.81 mg /kg, E₈₀ 67.05 s, ED₉₀ 17.56 mg /kg, E₉₀ 73.92 s. CONCLUSION: W0620 has an obviously antidepressant effect whereas it has no inhibition action on CNS. There is a sigmoid curvilinear relationship between the logarithmic doses and the antidepressant effects.