Introduction
cataplexy, daytime sleepiness, IH, behavioral abnormalities, sleepiness, sleep drunkenness, hypersomnia sleep-wake disorders, idiopathic CNS hypersomnolence
DISORDERS, CATAPLEXY, INSUFFICIENT SLEEP SYNDROME, PATHOPHYSIOLOGY, IDIOPATHIC HYPERSOMNIA
Idiopathic hypersomnia (IH), one of the central hypersomnia sleep-wake disorders, is characterized by chronic excessive daytime sleepiness (EDS) and sleep inertia (awakening that is difficult or accompanied by behavioral abnormalities; also called sleep drunkenness). People with IH may experience additional symptoms, such as prolonged night-time sleep and non-refreshing naps [Diagnostic criteria for IH, also termed idiopathic CNS hypersomnolence in the International Classification of Sleep Disorders—Edition 3 (ICSD-3) nosology, requires the presence of daytime lapses into sleep or an irrepressible need to sleep present on a daily basis for at least 3 months, the absence of cataplexy, fewer than two sleep-onset rapid eye movement (REM) periods (including nocturnal PSG [nPSG]) on a multiple sleep latency test (MSLT) and either an average sleep latency of ≤ 8 min on the MLST or a total 24-h sleep time of ≥ 660 min. Insufficient sleep syndrome and alternative causes for sleepiness must be excluded [The pathophysiology of IH is unknown. Although orexin (hypocretin), melanin-concentrating hormone, adenosine, acetylcholine, dopamine, norepinephrine, histamine, gamma-aminobutyric acid (GABA), and glutamate are known to be involved in sleep-wake regulation [Two orexin neuropeptides, orexin A and orexin B (also called hypocretin-1 and hypocretin-2) act through the G-protein coupled orexin-1 and orexin-2 receptors (OX1R and OX2R). In normal sleep-wake regulation, orexin is believed to play a key role in arousal/wakefulness stabilization [The aim of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of danavorexton administered to adults with IH.