董静文, 史源, 唐丽娜, 胡伟, 张建军. 化合物H1208镇静催眠作用研究J. 药学学报, 2014,49(6): 869-874.
引用本文: 董静文, 史源, 唐丽娜, 胡伟, 张建军. 化合物H1208镇静催眠作用研究J. 药学学报, 2014,49(6): 869-874.
DONG Jing-wen, SHI Yuan, TANG Li-na, HU Wei, ZHANG Jian-jun. Evaluation of the sedative and hypnotic effects of H1208J. Acta Pharmaceutica Sinica, 2014,49(6): 869-874.
Citation: DONG Jing-wen, SHI Yuan, TANG Li-na, HU Wei, ZHANG Jian-jun. Evaluation of the sedative and hypnotic effects of H1208J. Acta Pharmaceutica Sinica, 2014,49(6): 869-874.

化合物H1208镇静催眠作用研究

Evaluation of the sedative and hypnotic effects of H1208

  • 摘要: 研究化合物H1208对小鼠的镇静催眠作用,并对其机制进行初步探索。通过测定H1208对小鼠自主活动、睡眠潜伏期及睡眠持续时间的影响,评价其中枢镇静及催眠作用;通过监测小鼠脑电及肌电,分析H1208对睡眠成分的影响;并应用高效液相色谱-电化学检测法测定小鼠大脑皮层、纹状体及下丘脑内单胺类神经递质含量的变化。结果表明,与溶剂对照组比较,腹腔注射H1208(5和25 mg·kg-1,ip)能显著抑制小鼠的自主活动,抑制率分别为56.7% 和80.2%。H1208(30和60 mg·kg-1,ip)可诱导小鼠睡眠,增加非快动眼睡眠,缩短快动眼睡眠时间,显著降低小鼠纹状体和大脑皮层内多巴胺及大脑皮层内5-羟色胺含量。结果提示,H1208具有强效的镇静催眠作用;降低脑内神经递质多巴胺、5-羟色胺水平可能是其发挥镇静催眠作用的机制之一。

     

    Abstract: This study is to investigate the sedative and hypnotic effects of a novel compound H1208.The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice.Thehypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes.The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection.The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg·kg-1, ip) treated mice, respectively.The loss of righting reflex was directly induced in mice after H1208 (60 mg·kg-1, ip) administration.The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg·kg-1,ip) administration.However, the rapid eye movement sleep decreased significantly.The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly.These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.

     

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