Abstract
Insomnia is when a person feels difficulty falling asleep or staying asleep, often associated with complications, such as fatigue, sleepiness, etc. Insomnia may cause disruptions in daytime physical and mental abilities. Orexins or hypocretins are the neuropeptides secreted from the lateral hypothalamus and play a major role in the sleep-wake cycle through a complex interplay between wake-promoting and sleep-promoting neuronal systems. Orexin receptor antagonists (Orexants) are the new treatment options for insomnia disorder, narcolepsy, and other sleep disturbances. There are two classes of Orexants, namely those that bind selectively to a specific orexin receptor are selective orexin receptor antagonists (SORA), and the others that bind to both the orexin receptors are dual orexin receptor antagonists (DORA). The first DORA was almorexant but restricted in use and the other three approved DORAs, such as suvorexant, lemborexant, and daridorexant were approved by the FDA, and several other DORAs and SORAs are under various stages of discovery and clinical investigation. Among the labeled limitations, the currently approved Orexants are contraindicated in people with narcolepsy and are controlled substances owing to their misuse liability. The present review discussed the sleep-wake cycle, phases of a sleep cycle, orexins, and Orexants, and summarized the pharmacology of the three approved DORAs, a type of Orexants and their potential advantages and limitations of their use in pharmacotherapy of insomnia disorder.
Published Version
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