Suvorexant, Novel Dual Orexin Receptor Antagonist for Management of Insomnia: A Systematic Review

Insomnia is a serious medical and social problem, its prevalence in the general population ranges from 9 to 35% depending on the country and assessment method. Often, patients are subject to inappropriate and therefore dangerous pharmacotherapies that include prolonged administration of hypnotic drugs, benzodiazepines and other GABAA receptor modulators. This usually does not lead to a satisfactory improvement in patients’ clinical states and may cause lifelong drug dependence. Orexins/hypocretins are key neuropeptides responsible for regulating central arousal and reward circuits. Due to their interaction with the sleep–wake regulating neuronal population, they can activate vigilance-promoting regions and prevent unwanted sleep intrusions. Understanding the multiple orexin modulatory effects is crucial in the context of pathogenesis of insomnia and should lead to the development of novel treatments. An important step in this process was the synthesis of dual antagonists of orexin receptors. Two receptors respond to orexin signaling, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) with partially overlapping nervous system distributions. Suvorexant (MK-4305) is a potent, selective, and orally bioavailable antagonist of OX1R and OX2R currently under clinical investigation as a novel therapy for insomnia. This new pharmacological approach might be the most appropriate to treat insomnia. Consistent cross-species sleep/wake architecture changes produced by Suvorexant highlight a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia. This article reviews the management procedure of insomnia by using this novel drug Suvorexant.