Modafinil alleviates levodopa-induced excessive nighttime sleepiness and restores monoaminergic systems in a nocturnal animal model of Parkinson's disease
Modafinil alleviates levodopa-induced excessive nighttime sleepiness and restores monoaminergic systems in a nocturnal animal model of Parkinson's disease
复制标题
DOI：
10.1016/j.jphs.2018.03.005
复制
发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Nagai, Masahiro
中科院分区：
文献类型：
--
作者：
Ando, Rina;Choudhury, Mohammed Emamussalehin;Nagai, Masahiro
多巴胺能药物治疗导致过度的日间嗜睡（EDS），一些研究表明使用莫达非尼治疗帕金森病（PD）患者的过度日间嗜睡是有益的。我们研究了莫达非尼是否对MPTP治疗的小鼠夜间PD模型中左旋多巴诱导的夜间过度嗜睡（ENS）具有改善特性。我们对全天记录的EEG分析显示，莫达非尼可以减少左旋多巴药物治疗的夜间PD模型的ENS。因此，我们研究了莫达非尼后处理随后MPTP是否显示对脑的单胺含量的任何影响，并发现MPTP处理的小鼠的去甲肾上腺素（NA）浓度显著增加。在神经恢复背景下（损伤后5天），莫达非尼治疗后导致MPTP治疗小鼠纹状体多巴胺（DA）浓度增加。在这里，我们首次证实莫达非尼改善左旋多巴诱导的过度嗜睡和恢复单胺能系统。莫达非尼显示的觉醒和抗帕金森病作用表明，与多巴胺能药物联合使用，莫达非尼联合给药可能值得尝试抑制PD患者的过度日间嗜睡和进行性多巴胺能神经元丢失。(C)2018作者Elsevier B.V.代表日本药理学会制作和主办。
Treatment with dopaminergic agents result excessive daytime sleepiness (EDS) and some studies have shown the benefit of using modafinil for treating excessive daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether modafinil have ameliorative properties against levodopa induced excessive nighttime sleepiness (ENS) in MPTP-treated murine nocturnal PD model. Our EEG analyses of whole day recordings revealed that modafinil reduce ENS of this nocturnal PD models with levodopa medications. Therefore, we investigated whether, modafinil post-treatment followed by MPTP shows any effect on monoamine contents of brain and found to robustly increased noradrenaline (NA) concentration of MPTP treated mice. Modafinil post-treatment, in neurorestorative context (5 days post-lesion) led to increased striatal dopamine (DA) concentrations of MPTP-treated mice. Here, we first confirmed that modafinil ameliorates levodopa induced excessive sleepiness and restores monoaminergic systems. The arousal and anti-parkinsonian effects displayed by modafinil indicate that in combination with dopaminergic agents, modafinil co-administration may be worthwhile in trying to suppress the excessive daytime sleepiness and progressive dopaminergic neuron loss in PD. (C) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.