Good night and good luck: norepinephrine in sleep pharmacology.
Good night and good luck: norepinephrine in sleep pharmacology.
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DOI：
10.1016/j.bcp.2009.10.004
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发表时间：
2010-03-15
影响因子：
5.8
通讯作者：
Weinshenker, David
中科院分区：
文献类型：
--
作者：
Mitchell, Heather A.;Weinshenker, David
睡眠是一个重要的生物过程，通过多个大脑区域和神经调质之间的复杂相互作用来调节。由于睡眠障碍可能对健康和生活质量产生有害影响，因此已经开发了各种各样的药物疗法来治疗过度觉醒和过度嗜睡的状况。神经递质去甲肾上腺素（NE），通过其参与上升唤醒系统，影响许多促进觉醒和睡眠的药物的疗效。促醒药物如安非他明和莫达非尼增加NE的细胞外水平，增强沿着促醒途径的传输。GABA能促进睡眠的药物，如苯二氮卓类药物和苯二氮卓类药物，更特异性地作用于苯二氮卓类受体，增加GABA的活性，从而抑制NE和促进觉醒的途径。褪黑激素和相关化合物通过抑制大脑生物钟中神经元的活动来增加睡眠，NE影响褪黑激素的合成。抗组胺药阻断组胺的促醒作用，组胺与NE共享相互信号传导。许多影响NE信号传导的抗抑郁药也用于治疗失眠。最后，用于治疗心血管疾病的肾上腺素能拮抗剂具有相当大的镇静作用。因此，长期以来以其在维持一般唤醒中的作用而闻名的NE也是睡眠药理学中的关键角色。本综述的目的是考虑NE在唤醒和睡眠促进药物的行动框架内的大脑唤醒系统的作用。
Sleep is a crucial biological process is regulated through complex interactions between multiple brain regions and neuromodulators. As sleep disorders can have deleterious impacts on health and quality of life, a wide variety of pharmacotherapies have been developed to treat conditions of excessive wakefulness and excessive sleepiness. The neurotransmitter norepinephrine (NE), through its involvement in the ascending arousal system, impacts the efficacy of many wake- and sleep-promoting medications. Wake-promoting drugs such as amphetamine and modafinil increase extracellular levels of NE, enhancing transmission along the wake-promoting pathway. GABAergic sleep-promoting medications like benzodiazepines and benzodiazepine-like drugs that act more specifically on benzodiazepine receptors increase the activity of GABA, which inhibits NE and the wake-promoting pathway. Melatonin and related compounds increase sleep by suppressing the activity of the neurons in the brain’s circadian clock, and NE influences the synthesis of melatonin. Antihistamines block the wake-promoting effects of histamine, which shares reciprocal signaling with NE. Many antidepressants that affect the signaling of NE are also used for treatment of insomnia. Finally, adrenergic antagonists that are used to treat cardiovascular disorders have considerable sedative effects. Therefore, NE, long known for its role in maintaining general arousal, is also a crucial player in sleep pharmacology. The purpose of this review is to consider the role of NE in the actions of wake- and sleep-promoting drugs within the framework of the brain arousal systems.
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