{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:22:45Z","timestamp":1769581365985,"version":"3.49.0"},"reference-count":116,"publisher":"Frontiers Media SA","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Neurosci."],"DOI":"10.3389\/fnins.2014.00057","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T12:24:45Z","timestamp":1399379085000},"source":"Crossref","is-referenced-by-count":47,"title":["OX1 and OX2 orexin\/hypocretin receptor pharmacogenetics"],"prefix":"10.3389","volume":"8","author":[{"given":"Miles D.","family":"Thompson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri","family":"Xhaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Innocenzo","family":"Rainero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyrki P.","family":"Kukkonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.npep.2007.04.006","article-title":"Effects of rapid eye movement sleep deprivation on hypocretin neurons in the hypothalamus of a rat model of depression","volume":"41","author":"Allard","year":"2007","journal-title":"Neuropeptides"},{"key":"B2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0887-8994(92)90365-6","article-title":"Sleep disorders in Tourette syndrome: a primary or unrelated problem?","volume":"8","author":"Allen","year":"1992","journal-title":"Pediatr. Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/YPG.0b013e328341a3db","article-title":"Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene","volume":"21","author":"Annerbrink","year":"2011","journal-title":"Psychiatr. Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.brainres.2009.09.106","article-title":"Lateral hypothalamic orexin\/hypocretin neurons: a role in reward-seeking and addiction","volume":"1314","author":"Aston-Jones","year":"2010","journal-title":"Brain Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.bbr.2012.06.013","article-title":"Amygdalar excitatory\/inhibitory circuits interacting with orexinergic neurons influence differentially feeding behaviors in hamsters","volume":"234","author":"Avolio","year":"2012","journal-title":"Behav. Brain Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1212\/01.wnl.0000219765.95038.d7","article-title":"A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort","volume":"66","author":"Baumber","year":"2006","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.cden.2013.04.005","article-title":"Primary headache disorders","volume":"57","author":"Benoliel","year":"2013","journal-title":"Dent. Clin. North Am"},{"key":"B8","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0304-3959(00)00470-X","article-title":"Orexin-A, an hypothalamic peptide with analgesic properties","volume":"92","author":"Bingham","year":"2001","journal-title":"Pain"},{"key":"B9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.brainres.2009.11.054","article-title":"The role of hypocretin in driving arousal and goal-oriented behaviors","volume":"1314","author":"Boutrel","year":"2010","journal-title":"Brain Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.euroneuro.2007.01.005","article-title":"Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder","volume":"17","author":"Brundin","year":"2007","journal-title":"Eur. Neuropsychopharmacol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.tips.2005.01.004","article-title":"Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation","volume":"26","author":"Bulenger","year":"2005","journal-title":"Trends. Pharmacol. Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/S0092-8674(00)81973-X","article-title":"Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation","volume":"98","author":"Chemelli","year":"1999","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11910-004-0023-7","article-title":"Functional neuroimaging of primary headache disorders","volume":"4","author":"Cohen","year":"2004","journal-title":"Curr. Neurol. Neurosci. Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1136\/jnnp.70.2.192","article-title":"Decreased sleep quality and increased sleep related movements in patients with Tourette's syndrome","volume":"70","author":"Cohrs","year":"2001","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"5320","DOI":"10.1021\/jm100541c","article-title":"Discovery of the dual orexin receptor antagonist [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H -1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia","volume":"53","author":"Cox","year":"2010","journal-title":"J. Med. Chem"},{"key":"B16","doi-asserted-by":"publisher","first-page":"16726","DOI":"10.1074\/jbc.M111.223537","article-title":"Temporal profiling of orexin receptor-arrestin-ubiquitin complexes reveals differences between receptor subtypes","volume":"286","author":"Dalrymple","year":"2011","journal-title":"J. Biol. Chem"},{"key":"B17","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1073\/pnas.95.1.322","article-title":"The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity","volume":"95","author":"de Lecea","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1152\/japplphysiol.00075.2007","article-title":"Contribution of orexin in hypercapnic chemoreflex: evidence from genetic and pharmacological disruption and supplementation studies in mice","volume":"103","author":"Deng","year":"2007","journal-title":"J. Appl. Physiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3774","DOI":"10.1210\/en.2003-0274","article-title":"Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets","volume":"144","author":"Diano","year":"2003","journal-title":"Endocrinology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1124\/jpet.109.152009","article-title":"Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat","volume":"330","author":"Dugovic","year":"2009","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e26430","DOI":"10.1371\/journal.pone.0026430","article-title":"Dynein light chain Tctex-type 1 modulates orexin signaling through its interaction with orexin 1 receptor","volume":"6","author":"Duguay","year":"2011","journal-title":"PLoS ONE"},{"key":"B22","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1046\/j.1526-4610.2002.02226.x","article-title":"Familial cluster headache: a series of 186 index patients","volume":"42","author":"El Amrani","year":"2002","journal-title":"Headache"},{"key":"B23","doi-asserted-by":"publisher","first-page":"38812","DOI":"10.1074\/jbc.M602494200","article-title":"Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both ligand-dependent and -independent coordinated alterations of receptor localization and function","volume":"281","author":"Ellis","year":"2006","journal-title":"J. Biol. Chem"},{"issue":"8","key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00008","article-title":"Effects of a newly developed potent orexin-2 receptor-selective antagonist, compound 1 m, on sleep\/wakefulness states in mice","volume":"8","author":"Etori","year":"2014","journal-title":"Front. Neurosci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1177\/0269881106082899","article-title":"Changes in brain orexin levels in a rat model of depression induced by neonatal administration of clomipramine","volume":"22","author":"Feng","year":"2008","journal-title":"J. Psychopharmacol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1017\/S0012162200000839","article-title":"An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries","volume":"42","author":"Freeman","year":"2000","journal-title":"Dev. Med. Child Neurol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1007\/s12017-007-8001-2","article-title":"The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia","volume":"9","author":"Fukunaka","year":"2007","journal-title":"Neuromol. Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1212\/WNL.56.1.115","article-title":"A prepro-orexin gene polymorphism is associated with narcolepsy","volume":"56","author":"Gencik","year":"2001","journal-title":"Neurology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S1474-4422(02)00104-7","article-title":"Pathophysiology of cluster headache: a trigeminal autonomic cephalgia","volume":"1","author":"Goadsby","year":"2002","journal-title":"Lancet Neurol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"10911","DOI":"10.1073\/pnas.96.19.10911","article-title":"Orexin A activates locus coeruleus cell firing and increases arousal in the rat","volume":"96","author":"Hagan","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"B31","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1523\/JNEUROSCI.3258-04.2005","article-title":"The wake-promoting peptide orexin-B inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling","volume":"25","author":"Haj-Dahmane","year":"2005","journal-title":"J. Neurosci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.1021\/bi300136h","article-title":"Study of human Orexin-1 and -2 G-protein-coupled receptors with novel and published antagonists by modeling, molecular dynamics simulations, and site-directed mutagenesis","volume":"51","author":"Heifetz","year":"2012","journal-title":"Biochemistry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1176\/appi.ajp.158.10.1568","article-title":"A review and meta-analysis of the genetic epidemiology of anxiety disorders","volume":"158","author":"Hettema","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","first-page":"6570","DOI":"10.1074\/jbc.M407397200","article-title":"OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms","volume":"280","author":"Holmqvist","year":"2005","journal-title":"J. Biol. Chem"},{"key":"B35","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1096-9861(19991213)415:2<145::AID-CNE1>3.0.CO;2-2","article-title":"Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system","volume":"415","author":"Horvath","year":"1999","journal-title":"J. Comp. Neurol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nsmb.2504","article-title":"Crystal structure of oligomeric beta1-adrenergic G protein-coupled receptors in ligand-free basal state","volume":"20","author":"Huang","year":"2013","journal-title":"Nat. Struct. Mol. Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1101\/gr.161001","article-title":"Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines","volume":"11","author":"Hungs","year":"2001","journal-title":"Genome Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.neuroscience.2008.09.042","article-title":"I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation","volume":"157","author":"Ito","year":"2008","journal-title":"Neuroscience"},{"key":"B39","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/protein\/gzi004","article-title":"G protein-coupled receptors show unusual patterns of intrinsic unfolding","volume":"18","author":"Jaakola","year":"2005","journal-title":"Protein Eng. Des. Sel"},{"key":"B40","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.bbrc.2014.02.026","article-title":"Human orexin\/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors","volume":"445","author":"J\u00c3\u00a4ntti","year":"2014","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"B41","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1124\/mol.112.080523","article-title":"Autocrine endocannabinoid signaling potentiates orexin receptor signaling upon CB1 cannabinoid-OX1 orexin receptor coexpression","volume":"83","author":"J\u00c3\u00a4ntti","year":"2013","journal-title":"Mol. Pharmacol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1038\/npp.2012.38","article-title":"Activation of the orexin 1 receptor is a critical component of CO2-mediated anxiety and hypertension but not bradycardia","volume":"37","author":"Johnson","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.brainres.2005.03.007","article-title":"Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally-administered orexins in diabetic neuropathic pain model rats","volume":"1044","author":"Kajiyama","year":"2005","journal-title":"Brain Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.5665\/sleep.2870","article-title":"Orexin gene therapy restores the timing and maintenance of wakefulness in narcoleptic mice","volume":"36","author":"Kantor","year":"2013","journal-title":"Sleep"},{"key":"B45","doi-asserted-by":"publisher","first-page":"E1089","DOI":"10.1152\/ajpendo.00351.2004","article-title":"Food deprivation differentially modulates orexin receptor expression and signalling in the rat hypothalamus and adrenal cortex","volume":"288","author":"Karteris","year":"2005","journal-title":"Am. J. Physiol. Endocrinol. Metab"},{"key":"B46","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1210\/jcem.86.9.7849","article-title":"Expression and coupling characteristics of the crh and orexin type 2 receptors in human fetal adrenals","volume":"86","author":"Karteris","year":"2001","journal-title":"J. Clin. Endocrinol. Metab"},{"key":"B47","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00424-012-1080-4","article-title":"The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats","volume":"463","author":"Kis","year":"2012","journal-title":"Pflugers Arch"},{"key":"B48","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1515\/bmc-2012-0013","article-title":"Recent progress in orexin\/hypocretin physiology and pharmacology","volume":"3","author":"Kukkonen","year":"2012","journal-title":"Biomol. Concepts"},{"key":"B49","doi-asserted-by":"publisher","first-page":"C2","DOI":"10.1152\/ajpcell.00227.2012","article-title":"Physiology of the orexinergic\/hypocretinergic system: a revisit in 2012","volume":"304","author":"Kukkonen","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"C1567","DOI":"10.1152\/ajpcell.00055.2002","article-title":"Functions of the orexinergic\/hypocretinergic system","volume":"283","author":"Kukkonen","year":"2002","journal-title":"Am. J. Physiol. Cell. Physiol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/bph.12324","article-title":"Orexin\/hypocretin receptor signalling cascades","volume":"171","author":"Kukkonen","year":"2014","journal-title":"Br. J. Pharmacol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/S0006-8993(99)01884-3","article-title":"Orexins\/hypocretins regulate drinking behaviour","volume":"842","author":"Kunii","year":"1999","journal-title":"Brain Res"},{"key":"B53","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.resp.2008.03.011","article-title":"Orexinergic modulation of breathing across vigilance states","volume":"164","author":"Kuwaki","year":"2008","journal-title":"Respir. Physiol. Neurobiol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/bph.12296","article-title":"Orexin\/hypocretin receptor signalling: a functional perspective","volume":"171","author":"Leonard","year":"2014","journal-title":"Br. J. Pharmacol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1212\/WNL.56.9.1233","article-title":"Increased familial risk of cluster headache","volume":"56","author":"Leone","year":"2001","journal-title":"Neurology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"21655","DOI":"10.1074\/jbc.M302536200","article-title":"Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes","volume":"278","author":"Liang","year":"2003","journal-title":"J. Biol. Chem"},{"key":"B57","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/S0092-8674(00)81965-0","article-title":"The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene","volume":"98","author":"Lin","year":"1999","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/S0361-9230(01)00756-0","article-title":"Chronic central infusion of orexin-A increases arterial pressure in rats","volume":"57","author":"Lin","year":"2002","journal-title":"Brain Res. Bull"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6028","DOI":"10.1523\/JNEUROSCI.6069-10.2011","article-title":"Orexin gene transfer into zona incerta neurons suppresses muscle paralysis in narcoleptic mice","volume":"31","author":"Liu","year":"2011","journal-title":"J. Neurosci"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1093\/oxfordjournals.molbev.a004040","article-title":"Molecular evolution of the mammalian alpha 2B adrenergic receptor","volume":"19","author":"Madsen","year":"2002","journal-title":"Mol. Biol. Evol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.bcp.2005.12.021","article-title":"Agonist potency differentiates G protein activation and Ca2+ signalling by the orexin receptor type 1","volume":"71","author":"Magga","year":"2006","journal-title":"Biochem. Pharmacol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1124\/mol.110.064584","article-title":"Mapping the binding pocket of dual antagonist almorexant to human orexin 1 and orexin 2 receptors: comparison with the selective OX1 (SB-674042) and OX2 (EMPA) antagonists","volume":"78","author":"Malherbe","year":"2010","journal-title":"Mol. Pharmacol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/10561","article-title":"Correlation between structural and functional changes in brain in an idiopathic headache syndrome","volume":"5","author":"May","year":"1999","journal-title":"Nat. Med"},{"key":"B64","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0140-6736(98)02470-2","article-title":"Hypothalamic activation in cluster headache attacks","volume":"352","author":"May","year":"1998","journal-title":"Lancet"},{"key":"B65","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.biopsych.2005.04.015","article-title":"Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects","volume":"58","author":"Meerabux","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"B65a","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.biopsych.2011.05.027","article-title":"Do unexpected panic attacks occur spontaneously?","volume":"70","author":"Meuret","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"B66","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s40263-012-0036-8","article-title":"Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status","volume":"27","author":"Mieda","year":"2013","journal-title":"CNS Drugs"},{"key":"B67","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1042\/BJ20041745","article-title":"The sustainability of interactions between the orexin-1 receptor and beta-arrestin-2 is defined by a single C-terminal cluster of hydroxy amino acids and modulates the kinetics of ERK MAPK regulation","volume":"387","author":"Milasta","year":"2005","journal-title":"Biochem. J"},{"key":"B68","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s00213-010-1909-5","article-title":"Opposite roles of dopamine and orexin in quinpirole-induced excessive drinking: a rat model of psychotic polydipsia","volume":"211","author":"Milella","year":"2010","journal-title":"Psychopharmacology"},{"key":"B69","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1476-5381.2009.00169.x","article-title":"G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function","volume":"158","author":"Milligan","year":"2009","journal-title":"Br. J. Pharmacol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.pain.2005.08.024","article-title":"Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice","volume":"118","author":"Mobarakeh","year":"2005","journal-title":"Pain"},{"key":"B71","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/j.neuropharm.2009.08.009","article-title":"Monoaminergic neuronal changes in orexin deficient mice","volume":"58","author":"Mori","year":"2010","journal-title":"Neuropharmacology"},{"key":"B72","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0140-6736(99)05582-8","article-title":"Hypocretin (orexin) deficiency in human narcolepsy","volume":"355","author":"Nishino","year":"2000","journal-title":"Lancet"},{"key":"B73","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.1093\/nar\/gkg584","article-title":"Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs","volume":"31","author":"Obenauer","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1212\/WNL.57.10.1896","article-title":"Polymorphisms in hypocretin\/orexin pathway genes and narcolepsy","volume":"57","author":"Olafsdottir","year":"2001","journal-title":"Neurology"},{"key":"B75","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/WNR.0b013e3282f32d64","article-title":"Hypocretin-1\/orexin-A activates subfornical organ neurons of rats","volume":"19","author":"Ono","year":"2008","journal-title":"Neuroreport"},{"key":"B76","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1517\/14728214.2011.628313","article-title":"Emerging drugs for panic disorder","volume":"16","author":"Perna","year":"2011","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"B77","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/79690","article-title":"A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains","volume":"6","author":"Peyron","year":"2000","journal-title":"Nat. Med"},{"key":"B78","doi-asserted-by":"crossref","first-page":"9996","DOI":"10.1523\/JNEUROSCI.18-23-09996.1998","article-title":"Neurons containing hypocretin (orexin) project to multiple neuronal systems","volume":"18","author":"Peyron","year":"1998","journal-title":"J. Neurosci"},{"key":"B79","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s10194-005-0194-x","article-title":"Genetics of cluster headache: an update","volume":"6","author":"Pinessi","year":"2005","journal-title":"J. Headache Pain"},{"key":"B80","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.neulet.2011.10.061","article-title":"Mapping of the binding sites for the OX(1) orexin receptor antagonist, SB-334867, using orexin\/hypocretin receptor chimaeras","volume":"506","author":"Putula","year":"2012","journal-title":"Neurosci. Lett"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/j.febslet.2011.04.020","article-title":"Orexin\/hypocretin receptor chimaeras reveal structural features important for orexin peptide distinction","volume":"585","author":"Putula","year":"2011","journal-title":"FEBS Lett"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1111\/j.1526-4610.2008.01080.x","article-title":"Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache","volume":"48","author":"Rainero","year":"2008","journal-title":"Headache"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1212\/01.WNL.0000142424.65251.DB","article-title":"A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache","volume":"63","author":"Rainero","year":"2004","journal-title":"Neurology"},{"key":"B84","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.jad.2010.10.033","article-title":"Association between major mood disorders and the hypocretin receptor 1 gene","volume":"130","author":"Rainero","year":"2011a","journal-title":"J. Affect. Disord"},{"key":"B85","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s10194-011-0314-8","article-title":"Evidence for an association between migraine and the hypocretin receptor 1 gene","volume":"12","author":"Rainero","year":"2011b","journal-title":"J. Headache Pain"},{"key":"B86","doi-asserted-by":"publisher","first-page":"4808","DOI":"10.1210\/jc.86.10.4808","article-title":"Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis","volume":"86","author":"Randeva","year":"2001","journal-title":"J. Clin. Endocrinol. Metab"},{"key":"B87","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/nrm2803","article-title":"Fine-tuning of GPCR activity by receptor-interacting proteins","volume":"10","author":"Ritter","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0167-0115(00)00203-2","article-title":"Dose-response effects of orexin-A on food intake and the behavioural satiety sequence in rats","volume":"96","author":"Rodgers","year":"2000","journal-title":"Regul. Pept"},{"key":"B89","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S1474-4422(04)00735-5","article-title":"Epidemiology and genetics of cluster headache","volume":"3","author":"Russell","year":"2004","journal-title":"Lancet Neurol"},{"key":"B90","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1046\/j.1526-4610.1996.3610608.x","article-title":"Cluster headache is an inherited disorder in some families","volume":"36","author":"Russell","year":"1996","journal-title":"Headache"},{"key":"B91","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1046\/j.1365-2826.2001.00672.x","article-title":"The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats","volume":"13","author":"Russell","year":"2001","journal-title":"J. Neuroendocrinol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/S0092-8674(00)80949-6","article-title":"Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior","volume":"92","author":"Sakurai","year":"1998","journal-title":"Cell"},{"key":"B93","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/S0006-3223(02)01740-7","article-title":"Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects","volume":"54","author":"Salomon","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1212\/01.wnl.0000215852.35329.34","article-title":"Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene","volume":"66","author":"Sch\u00c3\u00bcrks","year":"2006","journal-title":"Neurology"},{"key":"B95","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/j.1468-2982.2007.01287.x","article-title":"The G1246A polymorphism in the hypocretin receptor 2 gene is not associated with treatment response in cluster headache","volume":"27","author":"Sch\u00c3\u00bcrks","year":"2007a","journal-title":"Cephalalgia"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1111\/j.1526-4610.2007.00863.x","article-title":"Association between migraine and the G1246A polymorphism in the hypocretin receptor 2 gene","volume":"47","author":"Sch\u00c3\u00bcrks","year":"2007b","journal-title":"Headache"},{"key":"B97","doi-asserted-by":"publisher","first-page":"G1182","DOI":"10.1152\/ajpgi.00218.2004","article-title":"Orexin-A does not stimulate food intake in old rats","volume":"287","author":"Takano","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.bbr.2010.09.028","article-title":"A role for hypocretin\/orexin in motivation","volume":"217","author":"Thompson","year":"2011","journal-title":"Behav. Brain Res"},{"key":"B99","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1080\/10408360591001895","article-title":"The G protein-coupled receptors: pharmacogenetics and disease","volume":"42","author":"Thompson","year":"2005","journal-title":"Crit. Rev. Clin. Lab. Sci"},{"key":"B100","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-1-59745-205-2_6","article-title":"Pharmacogenomics of G protein-coupled receptor signaling: insights from health and disease","volume":"448","author":"Thompson","year":"2008a","journal-title":"Methods Mol. Biol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1002\/ajmg.b.30047","article-title":"Variants of the orexin2\/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity","volume":"129","author":"Thompson","year":"2004","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet"},{"key":"B102","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1097\/WNR.0b013e32834e5af3","article-title":"Chromosome 1p36 in migraine with aura: association study of the 5HT(1D) locus","volume":"23","author":"Thompson","year":"2012","journal-title":"Neuroreport"},{"key":"B103","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/978-1-59745-205-2_7","article-title":"G protein-coupled receptors disrupted in human genetic disease","volume":"448","author":"Thompson","year":"2008b","journal-title":"Methods Mol. Biol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-1-59745-205-2_8","article-title":"G protein-coupled receptor pharmacogenetics","volume":"448","author":"Thompson","year":"2008c","journal-title":"Methods Mol. Biol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.ejphar.2011.05.074","article-title":"Chimeric, mutant orexin receptors show key interactions between orexin receptors, peptides and antagonists","volume":"667","author":"Tran","year":"2011","journal-title":"Eur. J. Pharmacol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1124\/mol.112.078063","article-title":"OX1 orexin\/hypocretin receptor signaling via arachidonic acid and endocannabinoid release","volume":"82","author":"Turunen","year":"2012","journal-title":"Mol. Pharmacol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"37414","DOI":"10.1074\/jbc.M111.287649","article-title":"Hetero-multimerization of the cannabinoid CB1 receptor and the orexin OX1 receptor generates a unique complex in which both protomers are regulated by orexin A","volume":"286","author":"Ward","year":"2011","journal-title":"J. Biol. Chem"},{"key":"B108","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/S0163-7258(98)00030-8","article-title":"Molecular basis of receptor\/G-protein-coupling selectivity","volume":"80","author":"Wess","year":"1998","journal-title":"Pharmacol. Ther"},{"key":"B109","doi-asserted-by":"publisher","first-page":"e28","DOI":"10.1017\/S1462399408000823","article-title":"Hypothalamic orexins\/hypocretins as regulators of breathing","volume":"10","author":"Williams","year":"2008","journal-title":"Expert Rev. Mol. Med"},{"key":"B111","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3109\/01677063.2011.566953","article-title":"Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist","volume":"25","author":"Winrow","year":"2011","journal-title":"J. Neurogenet"},{"key":"B110","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/bph.12261","article-title":"Discovery and development of orexin receptor antagonists as therapeutics for insomnia","volume":"171","author":"Winrow","year":"2014","journal-title":"Br. J. Pharmacol"},{"key":"B112","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1126\/science.1194396","article-title":"Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists","volume":"330","author":"Wu","year":"2010","journal-title":"Science"},{"key":"B113","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1042\/BJ20110230","article-title":"The orexin OX1 receptor exists predominantly as a homodimer in the basal state: potential regulation of receptor organization by both agonist and antagonist ligands","volume":"439","author":"Xu","year":"2011","journal-title":"Biochem. J"},{"key":"B114","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.neulet.2005.05.032","article-title":"Respiratory and cardiovascular actions of orexin-A in mice","volume":"385","author":"Zhang","year":"2005","journal-title":"Neurosci. Lett"},{"key":"B115","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/cne.20515","article-title":"Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function","volume":"485","author":"Zheng","year":"2005","journal-title":"J. Comp. Neurol"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"deposited":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T07:07:46Z","timestamp":1565420866000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fnins.2014.00057\/abstract"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,6]]},"references-count":116,"URL":"https:\/\/doi.org\/10.3389\/fnins.2014.00057","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,6]]}}}