TY - JOUR
T1 - Development of a Therapeutic Drug for Narcolepsy
AU - Irukayama-Tomobe, Yoko
AU - Yanagisawa, Masashi
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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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U2 - 10.11477/mf.1416201171
DO - 10.11477/mf.1416201171
M3 - Article
C2 - 30416119
AN - SCOPUS:85056314665
SN - 1881-6096
VL - 70
SP - 1255
EP - 1263
JO - Brain and nerve = Shinkei kenkyu no shinpo
JF - Brain and nerve = Shinkei kenkyu no shinpo
IS - 11
ER -