oreksiini

Oreksiini, also known as orexin or hypocretin, refers to two neuropeptides, orexin-A and orexin-B, produced by a group of neurons in the lateral hypothalamus and adjacent areas of the brain. These peptides exert their effects by binding to two G protein–coupled receptors, orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). The orexin-producing neurons project widely throughout the brain, including the cortex, thalamus, brainstem, and spinal cord, enabling broad influence over physiological states.

The orexin system plays a central role in promoting wakefulness and maintaining sustained arousal. It interacts with other wake-promoting systems, such as monoaminergic and cholinergic neurons, to stabilize wake states and regulate transitions between sleep and wake. Beyond arousal, orexins contribute to energy homeostasis by stimulating feeding and influencing metabolism, and they participate in reward processing, stress responses, autonomic control, and aspects of REM sleep regulation.

Clinical relevance is highlighted by narcolepsy type 1, in which there is a loss of orexin-producing neurons in the lateral hypothalamus. This leads to low or undetectable cerebrospinal fluid orexin-A levels and symptoms such as excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Treatments targeting the orexin system include orexin receptor antagonists, such as suvorexant and lemborexant, approved for insomnia; these drugs promote sleep by blocking wake-promoting signaling. Conversely, research into orexin agonists aims to restore orexin signaling in narcolepsy and other conditions, though such therapies are not yet approved. The orexin system remains a focus of study for its roles in sleep, metabolism, and motivational processes.