hypocretin-1

Hypocretin-1 (also known as orexin-A) is an endogenous 33-amino-acid neuropeptide that acts as a dual agonist at the orexin receptors HCRTR1 (OX1R) and HCRTR2 (OX2R). Produced by neurons in the lateral hypothalamus, hypocretin-1 is a master regulator of the sleep-wake cycle, arousal, and energy homeostasis. Deficiency of hypocretin-1 is the primary cause of narcolepsy type 1 (narcolepsy with cataplexy). Because peripherally administered hypocretin-1 has poor blood-brain barrier penetrance, researchers have investigated intranasal delivery to bypass the blood-brain barrier and deliver the peptide directly to the central nervous system. In small, academic, placebo-controlled clinical studies, intranasal administration of hypocretin-1 in patients with narcolepsy type 1 has been shown to stabilize REM sleep, reduce wake-to-REM transitions, improve attention, and restore olfactory function. It has also been explored for reversing the cognitive effects of sleep deprivation. However, no commercial developer has advanced the peptide into late-stage clinical development, and therapeutic focus has largely shifted to oral small-molecule orexin receptor agonists.

Other names

Hcrt 1Hcrt1Hcrt-1hypocretin 1hypocretin1hypocretin-1orexin Aorexin-A