The orexin story, sleep and sleep disturbances

Abstract

Summary The orexins, also known as hypocretins, are two neuropeptides (orexin A and B or hypocretin 1 and 2) produced by a few thousand neurons located in the lateral hypothalamus that were independently discovered by two research groups in 1998. Those two peptides bind two receptors (orexin/hypocretin receptor 1 and receptor 2) that are widely distributed in the brain and involved in the central physiological regulation of sleep and wakefulness, orexin receptor 2 having the major role in the maintenance of arousal. They are also implicated in a multiplicity of other functions, such as reward seeking, energy balance, autonomic regulation and emotional behaviours. The destruction of orexin neurons is responsible for the sleep disorder narcolepsy with cataplexy (type 1) in humans, and a defect of orexin signalling also causes a narcoleptic phenotype in several animal species. Orexin discovery is unprecedented in the history of sleep research, and pharmacological manipulations of orexin may have multiple therapeutic applications. Several orexin receptor antagonists were recently developed as new drugs for insomnia, and orexin agonists may be the next‐generation drugs for narcolepsy. Given the broad range of functions of the orexin system, these drugs might also be beneficial for treating various conditions other than sleep disorders in the near future.

Narcolepsy—A Neuropathological Obscure Sleep Disorder: A Narrative Review of Current Literature

“…In addition, thyrotrophin-releasing hormone and the nicotine patch are both promising new treatments for narcolepsy. Future research is required to validate and establish future treatment options as effective therapeutic strategies for narcolepsy [ 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ]. Table 1 contains a list of potential therapeutics that may help with narcolepsy symptoms.…”

Novel 3-Aminopyrrolidine and Piperidine Macrocyclic Orexin Receptor Agonists for Treating Sleep Disorders

“…The following table shows representative compounds tested for human orexin-2 receptor agonists activity and the biological data obtained from testing representative examples. …”

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury

“…Orexins (orexin A and orexin B) are hypothalamic neuropeptides that regulate the sleep-wake cycle [ 5 ]. The activity of orexin neurons increases during wakefulness and decreases during sleep.…”

“…The activity of orexin neurons increases during wakefulness and decreases during sleep. The loss of orexin neurons in humans has been known to be associated with narcolepsy, which is a chronic sleep disorder characterized by excessive daytime sleepiness [ 5 ]. Orexins also play an important role in the regulation of the neuroendocrine and autonomic nervous systems [ 5 , 6 ].…”

“…The loss of orexin neurons in humans has been known to be associated with narcolepsy, which is a chronic sleep disorder characterized by excessive daytime sleepiness [ 5 ]. Orexins also play an important role in the regulation of the neuroendocrine and autonomic nervous systems [ 5 , 6 ]. Orexins act on two G-protein-coupled receptors, orexin receptor type 1 and type 2 [ 7 ].…”