Orexin receptors: a journey through their discovery to the development of suvorexant, the new sleeping pill

Anandabaskar Nishanthi, Mourouguessine Vimal, Selvarajan Sandhiya, Steven Aibor Dkhar


Orexin (OX) neuropeptides acting through G-protein coupled OX1 and OX2 receptors are implicated in a variety of physiological roles including regulation of feeding, sleep-wake cycle, energy metabolism and reward pathways. Accumulating experimental evidence indicates that orexins are wake promoting neuropeptides and deficits in orexinergic neurotransmission leads to narcolepsy, a debilitating sleep disorder. This has led to a search for orexin receptor agonists for pharmacotherapy of narcolepsy. However, development of orexin receptor agonists are still in their infancy stage and it invokes further research to know whether it could turn into a reality. In addition, the role of orexin neuropeptides in promoting arousal and wakefulness has generated considerable interest in developing orexin receptor antagonists for treatment of insomnia. This quest was accomplished with the approval of suvorexant by United States food and drug administration in 2014. This remarkable discovery has opened a novel approach for treatment of insomnia through neuromodulation of orexin signaling. Hence this review focuses on the orexinergic system, their physiological action and potential role as pharmacological targets.


OX receptors, Hypocretin receptors, Insomnia, Suvorexant, Neuropeptide

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