Orexin A and orexin B are hypothalamic neuropeptides initially identified as 
endogenous ligands for two orphan G-protein coupled receptors (GPCRs). They play 
critical roles in the maintenance of wakefulness by regulating function of 
monoaminergic and cholinergic neurons that are implicated in the regulation of 
wakefulness. Loss of orexin neurons in humans is associated with narcolepsy, a 
sleep disorder characterized by excessive daytime sleepiness and cataplexy, 
further suggesting the particular importance of orexin in the maintenance of the 
wakefulness state. These findings have encouraged pharmaceutical companies to 
develop drugs targeting orexin receptors as novel medications of sleep 
disorders, such as narcolepsy and insomnia. Indeed, phase III clinical trials 
were completed last year of suvorexant, a non-selective (dual) antagonist for 
orexin receptors, for the treatment of primary insomnia, and demonstrate 
promising results. The New Drug Application (NDA) for suvorexant has been 
submitted to the US FDA. Thus, the discovery of a critical role played by the 
orexin system in the regulation of sleep/wakefulness has opened the door of a 
new era for sleep medicine.