title: Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.
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.
authors.affiliation: Department of Histology and Embryology, Medical University of Silesia, Katowice, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Pałasz
authors.forename: Damien
authors.initials: D
authors.lastname: Lapray
authors.forename: Christelle
authors.initials: C
authors.lastname: Peyron
authors.forename: Ewa
authors.initials: E
authors.lastname: Rojczyk-Gołębiewska
authors.forename: Rafał
authors.initials: R
authors.lastname: Skowronek
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Markowski
authors.forename: Beata
authors.initials: B
authors.lastname: Czajkowska
authors.forename: Marek
authors.initials: M
authors.lastname: Krzystanek
authors.forename: Ryszard
authors.initials: R
authors.lastname: Wiaderkiewicz
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use*; D001572:Benzofurans / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000502:physiology; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013844:Thiazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D000081:Acetamides; D001381:Azepines; D001572:Benzofurans; D007546:Isoquinolines; C573816:MK-6096; C557781:N-((1-((5-(4-fluorophenyl)-2-methyl-4-thiazolyl)carbonyl)-2-piperidinyl)methyl)-4-benzofurancarboxamide; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D010880:Piperidines; D011743:Pyrimidines; D013844:Thiazoles; D014230:Triazoles; C551624:suvorexant; C519150:almorexant