吲哚衍生物I_(20)的抗焦虑作用及机制研究

The anxiolytic effect and mechanism of indole derivate I_(20)

目的 研究外周型苯二氮卓受体配基吲哚衍生物I2 0的抗焦虑作用及作用机制。方法 在小鼠高架十字迷宫模型和小鼠明暗箱模型上评价I2 0 的抗焦虑活性 ,用放免法测定给予不同剂量的I2 0 在不同时间点大鼠血清中神经类固醇孕酮的含量。结果 I2 0 (1mg·kg-1,ip)能增加小鼠在开臂内运动时间百分率和小鼠穿箱次数 ,在小鼠高架十字迷宫与明暗箱模型上显示出抗焦虑作用 ;I2 0 在实验剂量下 (2 0mg·kg-1,ip)对小鼠自主活动性无影响 ,表明该化合物在抗焦虑的剂量下无镇静的副作用。放免测定结果表明 ,I2 0 能剂量依赖与时间依赖地增加大鼠血清中孕酮的含量。结论 I2 0 可能是通过与外周型苯二氮卓受体结合 ,增加体内神经类固醇孕酮的释放 ,间接调控GABAA

AIM To investigate the anxiolytic effect and mechanism of action of the indo derivative I 20 ,a ligand of the peripheral benzodiazepine receptor. METHODS The anxiolytic effect was tested in the elevated plus maze and the light dark box. The content of progesterone in the rat plasma after injection of various doses of drugs in different time points was measured by radio immunoassay . RESULTS Compound I 20 (1 mg·kg -1 , ip) exhibited the anxiolytic effect in mice by increasing the time percentage into the open arms in the elevated plus maze and the number of transitions in the light dark box. I 20 failed to affect the locomotor activity in mice in the test dose(20 mg·kg -1 ,ip),suggesting I 20 did not induce sedation in the anxiolytic doses. I 20 induced a dose dependent and time dependent increase in the concentrations of the neurosteroid (progesterone) in the rat plasma. CONCLUSION The indole derivative I 20 may produce anxiolytic like effect by interacting with the PBR receptor, promoting the biosynthesis of neurosteroid progesterone and modulating the GABA A function indirectly.