Development of a Therapeutic Drug for Narcolepsy

Yoko Irukayama-Tomobe, Masashi Yanagisawa

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1255-1263
Number of pages9
JournalBrain and nerve = Shinkei kenkyu no shinpo
Volume70
Issue number11
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Clinical Neurology

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