Anticonvulsant effects of the selective melatonin receptor agonist ramelteon
Anticonvulsant effects of the selective melatonin receptor agonist ramelteon
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DOI：
10.1016/j.yebeh.2009.07.022
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发表时间：
2009-09-01
影响因子：
2.6
通讯作者：
Maganti, Rama
中科院分区：
文献类型：
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作者：
Fenoglio-Simeone, Kristina;Mazarati, Andrey;Maganti, Rama
目的：内源性褪黑激素先前已被证明在各种实验模型中发挥抗惊厥作用。因此，我们问是否雷美替安，一种合成的和选择性的褪黑激素受体激动剂，也可能具有抗惊厥和/或antiepileptogenicproperty.Methods：雷美替安（30或100 mg/kg，每天两次，连续5天）的影响进行了评估，在两种动物模型的癫痫。在大鼠快速点燃模型中，测量点燃动物的基线海马后放电特性、点燃进展和海马兴奋性。在未治疗的点燃大鼠中急性给药后评估抗癫痫发作的疗效。在自发性癫痫Kcna 1基因敲除小鼠模型中，我们使用连续视频/EEG监测72小时以上来确定癫痫发作频率和周期性。此外，昼夜节律的休息活动节律的ramelteon治疗的动物进行了研究与actigraph.Results：在点燃的动物，ramelteon逆转点燃诱导的海马兴奋性，但是，它没有修改基线后放电特性，进展和建立点燃状态的快速点燃模型。然而，在Kcna 1-null小鼠，雷美替酮（200 mg/kg/天）显着衰减癫痫发作的周期性和频率和改善昼夜休息活动节律与control animals.Conclusions相比：选择性褪黑素受体激动剂雷美替酮具有抗惊厥特性的慢性癫痫模型。我们的研究结果为褪黑激素受体成为抗惊厥药物开发的潜在新靶点提供了进一步的支持。(c)2009 Elsevier Inc. All rights reserved.
Objective: The endogenous hormone melatonin has previously been shown to exert anticonvulsant effects in a variety of experimental models. Accordingly, we asked whether ramelteon, a synthetic and selective melatonin receptor agonist, might also possess anticonvulsant and/or antiepileptogenic properties.Methods: The effects of ramelteon (30 or 100 mg/kg intraperitoneally twice daily for 5 days) were evaluated in two animal models of epilepsy. In the rat rapid kindling model, baseline hippocampal after discharge properties, kindling progression, and hippocampal excitability in kindled animals were measured. Anti-ictogenic efficacy was assessed after acute administration in untreated kindled rats. In the spontaneously epileptic Kcna1-null mouse model, we determined seizure frequency and periodicity using continuous video/EEG monitoring over 72 hours. Further, circadian rest-activity rhythms in ramelteon-treated animals were studied with actigraphy.Results: In kindled animals, ramelteon reversed kindling-induced hippocampal excitability; however, it did not modify baseline afterdischarge properties, the progression and establishment of the kindled state in the rapid kindling model. However, in Kcna1-null mice, ramelteon (200 mg/kg/day) significantly attenuated seizure periodicity and frequency and improved circadian rest-activity rhythms compared with control animals.Conclusions: The selective melatonin receptor agonist ramelteon possesses anticonvulsant properties in a chronic epilepsy model. Our findings provide further support for melatonin receptors being potential novel targets for anticonvulsant drug development. (c) 2009 Elsevier Inc. All rights reserved.