Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.

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Palasz A, Lapray D, Peyron C, Rojczyk-Golebiewska E, Skowronek R, Markowski G, Czajkowska B, Krzystanek M, Wiaderkiewicz R

Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.

Int J Neuropsychopharmacol. 2014 Jan;17(1):157-68. doi: 10.1017/S1461145713000552. Epub 2013 May 23.

PubMed ID
23702225 [ View in PubMed
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Abstract

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. Brain state transitions require the coordinated activity of numerous neuronal pathways and brain structures. It is thought that orexin-expressing neurons play a crucial role in this process. 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. Crucially, these drugs, as opposed to benzodiazepines, do not change the sleep architecture and have limited side-effects. This new pharmacological approach might be the most appropriate to treat insomnia.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
SuvorexantOrexin receptor type 1ProteinHumans
Yes
Antagonist
Details
SuvorexantOrexin receptor type 2ProteinHumans
Yes
Antagonist
Details