Sleep-promoting action of IIK7, a selective MT2 melatonin receptor agonist in the rat
Sleep-promoting action of IIK7, a selective MT2 melatonin receptor agonist in the rat
复制标题
DOI：
10.1016/j.neulet.2009.04.005
复制
发表时间：
2009-06-26
影响因子：
2.5
通讯作者：
Sugden, David
中科院分区：
文献类型：
--
作者：
Fisher, Simon P.;Sugden, David
除了褪黑激素本身的各种制剂外，几种新型褪黑激素受体激动剂可用于或正在开发用于治疗抑郁症。褪黑激素被认为主要通过两种高亲和力的G蛋白偶联受体MT和MT 2发挥其作用，尽管尚不清楚哪种亚型负责促进睡眠的作用。本研究采用无线电遥测记录EEG和EMG在不受限制的自由活动的大鼠监测的睡眠-觉醒行为，并研究了急性睡眠促进活动的MT 2受体亚型选择性褪黑激素类似物，IIK 7。IIK 7是MT 2受体亚型的完全激动剂，但却是MT 1受体的部分激动剂，对MT 2的亲和力比MT 1高90倍。与褪黑激素一样，IIK 7（10 mg/kg i. p.）显著降低NREM睡眠起始潜伏期，短暂增加NREM睡眠时间，但不改变REM睡眠潜伏期或REM睡眠量。EEG功率谱的分析显示在IIK 7给药后δ（1-4 Hz）或θ活动（5-8 Hz）没有变化。与溶剂处理的大鼠相比，IIK 7使核心体温略微降低（类似于0.3 ℃）。睡眠-觉醒周期中的急性和短暂变化模拟了褪黑激素的变化，并表明其促进睡眠的活性是由MT 2受体亚型的激活介导的。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Several novel melatonin receptor agonists, in addition to various formulations of melatonin itself, are either available or in development for the treatment ofinsomnia. Melatonin is thought to exert its effects principally through two high affinity, G-protein coupled receptors, MT, and MT2, though it is not known which subtype is responsible for the sleep-promoting action. The present study used radiotelemetry to record EEG and EMG in un-restrained freely moving rats to monitor the sleep-wake behaviour and examined the acute sleep-promoting activity of an MT2 receptor subtype selective melatonin analog, IIK7. IIK7 is a full agonist at the MT2 receptor subtype but a partial agonist at the MT, receptor and has similar to 90-fold higher affinity for MT2 than MT1. Like melatonin, IIK7 (10 mg/kg i.p.) significantly reduced NREM sleep onset latency and transiently increased the time spent in NREM sleep, but did not alter REM sleep latency or the amount of REM sleep. An analysis of the EEG power spectrum showed no change in delta (1-4 Hz) or theta activity (5-8 Hz) following IIK7 administration. Core body temperature was slightly decreased (similar to 0.3 degrees C) by IIK7 compared to vehicle-treated rats. The acute and transient changes in the sleep-wake cycle mimic the changes seen with melatonin and suggest that its sleep-promoting activity is mediated by activation of the MT2 receptor subtype. (C) 2009 Elsevier Ireland Ltd. All rights reserved.