BRAIN and NERVE Shinkei Kenkyu no Shinpo Volume 70, Issue 11 (November 2018)

Development of a Therapeutic Drug for Narcolepsy Yoko Irukayama-Tomobe 1 , Masashi Yanagisawa 1 1International Institute for Integrative Sleep Medicine Keyword: 日中の過度の眠気 , 脳波検査 , 筋電図 , G蛋白共役型受容体 , 生理活性ペプチド , excessive daytime sleepiness , electroencephalography , electromyography , G-protein-coupled receptors , neuropeptide pp.1255-1263
Published Date 2018/11/1
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Narcolepsy-cataplexy is a debilitating disorder characterized by excessive daytime sleepiness and cataplexy, a bilateral loss of muscle tone triggered by positive emotions. The disease is caused by the loss of orexin-producing neurons in the hypothalamus. Currently, only symptom-oriented therapies are available for narcolepsy. We have recently discovered a potent, non-peptide orexin type-2 receptor (OX2R) agonist, YNT-185. We show that peripheral administration of YNT-185 significantly ameliorated the narcolepsy symptoms in a mouse model for narcolepsy. No desensitization was observed after repeated administration of YNT-185 with respect to the suppression of cataplexy-like episodes. These results provide a proof -of-concept for mechanistic therapy for narcolepsy-cataplexy using OX2R agonists. Additionally, YNT-185 promoted wakefulness in wild-type mice, suggesting that orexin receptor agonists may be useful for the treatment of excessive daytime sleepiness due to other conditions, such as sleepiness accompanying depression and sleepiness due to side effects of medicines or jet lag/shift work.

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BRAIN and NERVE-神経研究の進歩
70巻11号 (2018年11月)
電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院