Mignot Emmanuel, Nishino Seiji
Howard Hughes Medical Research Institute, Stanford University School of Medicine, Stanford, CA, USA.
Sleep. 2005 Jun;28(6):754-63. doi: 10.1093/sleep/28.6.754.
In the past, narcolepsy was primarily treated using amphetamine-like stimulants and tricyclic antidepressants. Newer and novel agents, such as the wake-promoting compound modafinil and more selective reuptake inhibitors targeting the adrenergic, dopaminergic, and/or serotoninergic reuptake sites (ie, venlafaxine, atomoxetine) are better-tolerated available alternatives. The development of these agents, together with sodium oxybate (a slow-wave sleep-enhancing agent that consolidates nocturnal sleep, reduces cataplexy, and improves sleepiness), has led to improved functioning and quality of life for many patients with the disorder. However, these treatments are all symptomatically based and do not target hypocretin, a major neurotransmitter involved in the pathophysiology of narcolepsy. In this review, we discuss emerging therapies in the area of narcolepsy. These include novel antidepressant or anticataplectic, wake-promoting, and hypnotic compounds. We also report on novel strategies designed to compensate for hypocretin deficiency and on the use of immunosupression at the time of narcolepsy onset.
过去，发作性睡病主要使用苯丙胺类兴奋剂和三环类抗抑郁药进行治疗。新型药物，如促觉醒化合物莫达非尼以及更具选择性的针对肾上腺素能、多巴胺能和/或5-羟色胺能再摄取位点的再摄取抑制剂（即文拉法辛、托莫西汀），是耐受性更好的可用替代药物。这些药物的研发，连同羟丁酸钠（一种增强慢波睡眠、巩固夜间睡眠、减少猝倒并改善嗜睡的药物），使许多患有该疾病的患者的功能和生活质量得到了改善。然而，这些治疗均基于症状，并未针对发作性睡病病理生理学中涉及的主要神经递质下丘脑分泌素。在本综述中，我们讨论了发作性睡病领域的新兴疗法。这些疗法包括新型抗抑郁药或抗猝倒药、促觉醒化合物和催眠化合物。我们还报告了旨在弥补下丘脑分泌素缺乏的新策略以及发作性睡病发作时免疫抑制的使用情况。
