ARN-776

ARN-776 is a **small molecule agonist** of the **hypocretin/orexin receptor 2 (HCRTR2, also known as OX2R)**. It has shown efficacy in preclinical models of narcolepsy, increasing wakefulness and reducing cataplexy in orexin-deficient (narcoleptic) mice. ARN-776 produces dose-dependent increases in wakefulness, reduces non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and decreases cataplexy episodes. Its wake-promoting and sleep-suppressing actions are associated with increased EEG gamma band activity and hyperactivity. ARN-776 displays **limited blood-brain barrier penetration**, but still achieves significant physiological effects in vivo. It is investigated alongside TAK-925, another HCRTR2 agonist, as a potential therapy for narcolepsy and related sleep disorders[1][3][4][8].