{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T04:23:59Z","timestamp":1772511839333,"version":"3.50.1"},"reference-count":85,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["bmn.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Discovery Today"],"published-print":{"date-parts":[[2014,5]]},"DOI":"10.1016\/j.drudis.2014.01.001","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T17:15:36Z","timestamp":1389287736000},"page":"701-708","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"title":["Selective targets for arousal-modifying drugs: implications for the treatment of sleep disorders"],"prefix":"10.1016","volume":"19","author":[{"given":"Elemer","family":"Szabadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.drudis.2014.01.001_bib0005","series-title":"Neuropsychiatry and Behavioural Neurology Explained","year":"2004"},{"key":"10.1016\/j.drudis.2014.01.001_bib0010","series-title":"International Classification of Sleep Disorders: Diagnostic and Coding Manuel","author":"American Academy of Sleep Medicine","year":"2005"},{"key":"10.1016\/j.drudis.2014.01.001_bib0015","series-title":"Electrodiagnosis in Clinical Neurology","first-page":"41","article-title":"Electroencephalography: general principles and clinical applications","author":"Aminoff","year":"1992"},{"key":"10.1016\/j.drudis.2014.01.001_bib0020","series-title":"The Pharmacological Basis of Therapeutics","first-page":"47","article-title":"Drugs acting on the central nervous system: introduction","author":"Franz","year":"1975"},{"key":"10.1016\/j.drudis.2014.01.001_bib0025","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1111\/j.1460-9568.2009.06722.x","article-title":"Alternating vigilance states: new insights regarding neuronal networks and mechanisms","volume":"29","author":"Fort","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0030","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tips.2005.09.009","article-title":"From waking to sleeping: neuronal and chemical substrates","volume":"26","author":"Jones","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0035","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00018-011-0631-8","article-title":"The waking brain: an update","volume":"68","author":"Lin","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0040","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/j.1365-2125.2006.02680.x","article-title":"Drugs for sleep disorders: mechanisms and therapeutic prospects","volume":"61","author":"Szabadi","year":"2006","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0045","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00424-011-0996-4","article-title":"Waking with the hypothalamus","volume":"463","author":"Haas","year":"2012","journal-title":"Pflugers. Arch. Eur. J. Physiol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0050","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0079-6123(08)00929-1","article-title":"The roles of dopamine and serotonin, and their receptors, in regulating sleep and waking","volume":"172","author":"Monti","year":"2008","journal-title":"Prog. Brain Res."},{"key":"10.1016\/j.drudis.2014.01.001_bib0055","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1113\/jphysiol.2007.140160","article-title":"The pontine REM switch: past and present","volume":"584","author":"Fuller","year":"2007","journal-title":"J. Physiol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0060","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.sleep.2007.03.005","article-title":"Neurobiology of REM and NREM sleep","volume":"8","author":"McCarley","year":"2007","journal-title":"Sleep Med."},{"key":"10.1016\/j.drudis.2014.01.001_bib0065","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nature04767","article-title":"A putative flip\u2013flop switch for control of REM sleep","volume":"441","author":"Lu","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2014.01.001_bib0070","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00424-011-1054-y","article-title":"Brainstem mechanisms of paradoxical (REM) sleep generation","volume":"463","author":"Luppi","year":"2012","journal-title":"Pflugers Arch."},{"key":"10.1016\/j.drudis.2014.01.001_bib0075","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.neuron.2010.11.032","article-title":"Sleep state switching","volume":"68","author":"Saper","year":"2010","journal-title":"Neuron"},{"key":"10.1016\/j.drudis.2014.01.001_bib0080","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1152\/physrev.00032.2011","article-title":"Control of sleep and wakefulness","volume":"92","author":"Brown","year":"2012","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0085","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/cne.22559","article-title":"Reassessment of the structural basis of the ascending arousal system","volume":"519","author":"Fuller","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0090","doi-asserted-by":"crossref","first-page":"13244","DOI":"10.1523\/JNEUROSCI.5933-11.2012","article-title":"Histamine release in the basal forebrain mediates cortical activation through cholinergic neurons","volume":"32","author":"Zant","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0095","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/jsr.12061","article-title":"Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline","volume":"22","author":"Lelkes","year":"2013","journal-title":"J. Sleep Res."},{"key":"10.1016\/j.drudis.2014.01.001_bib0100","doi-asserted-by":"crossref","first-page":"11828","DOI":"10.1523\/JNEUROSCI.1259-09.2009","article-title":"Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep\u2013wake cycle","volume":"29","author":"Hassani","year":"2009","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0105","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/0269881113490326","article-title":"Functional neuroanatomy of the central noradrenergic system","volume":"27","author":"Szabadi","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0110","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2174\/157015908785777229","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function, Part I: principles of functional organisation","volume":"6","author":"Samuels","year":"2008","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0115","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.smrv.2010.11.003","article-title":"Serotonin control of sleep\u2013wake behaviour","volume":"15","author":"Monti","year":"2011","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0120","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuropharm.2012.06.036","article-title":"Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil","volume":"664","author":"Niepel","year":"2013","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.drudis.2014.01.001_bib0125","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/nature04284","article-title":"Hypothalamic regulation of sleep and circadian rhythms","volume":"437","author":"Saper","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2014.01.001_bib0130","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1124\/jpet.103.051797","article-title":"The novel melatonin agonist agomelatine (S20098) is an antagonist at 5HT2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways","volume":"306","author":"Millan","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.drudis.2014.01.001_bib0135","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1073\/pnas.0811400106","article-title":"Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep\u2013wake cycle","volume":"106","author":"Hassani","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.drudis.2014.01.001_bib0140","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.smrv.2012.10.002","article-title":"Melanin-concentrating hormone control of sleep\u2013wake behavior","volume":"17","author":"Monti","year":"2013","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0145","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrn2092","article-title":"The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness","volume":"8","author":"Sakurai","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0150","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/157015908785777193","article-title":"Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function, Part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans","volume":"6","author":"Samuels","year":"2008","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0155","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1046\/j.1460-9568.2000.00202.x","article-title":"Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin","volume":"12","author":"Kalsbeek","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0160","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1177\/0748730406293854","article-title":"SCN outputs and the hypothalamic balance of life","volume":"21","author":"Kalsbeek","year":"2006","journal-title":"J. Biol. Rhythms"},{"key":"10.1016\/j.drudis.2014.01.001_bib0165","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.brainresrev.2005.01.005","article-title":"Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus","volume":"49","author":"Mistlberger","year":"2005","journal-title":"Brain Res. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0170","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1046\/j.1460-9568.2002.02196.x","article-title":"Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract-tracing study in rat","volume":"16","author":"Deurveilher","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0175","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.neuroscience.2004.08.030","article-title":"Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state","volume":"130","author":"Deurveilher","year":"2005","journal-title":"Neuroscience"},{"key":"10.1016\/j.drudis.2014.01.001_bib0180","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.1523\/JNEUROSCI.23-18-07093.2003","article-title":"A broad role for melanopsin in nonvisual photoreception","volume":"23","author":"Gooley","year":"2003","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2014.01.001_bib0185","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1177\/0748730406294627","article-title":"Neurobiology of the sleep\u2013wake cycle: sleep architecture, circadian regulation, and regulatory feedback","volume":"21","author":"Fuller","year":"2006","journal-title":"J. Biol. Rhythms"},{"issue":"Suppl. 1","key":"10.1016\/j.drudis.2014.01.001_bib0190","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S1389-9457(05)80002-4","article-title":"Brain structures and receptors involved in alertness","volume":"6","author":"Aston-Jones","year":"2005","journal-title":"Sleep Med."},{"key":"10.1016\/j.drudis.2014.01.001_bib0195","doi-asserted-by":"crossref","first-page":"e1247","DOI":"10.1371\/journal.pone.0001247","article-title":"Brain responses to violet, blue and green monochromatic light exposures in humans: prominent role of blue light and the brainstem","volume":"11","author":"Vandewalle","year":"2007","journal-title":"PLoS ONE"},{"key":"10.1016\/j.drudis.2014.01.001_bib0200","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.smrv.2007.07.009","article-title":"Alerting effects of light","volume":"11","author":"Cajochen","year":"2007","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0205","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.neuroscience.2012.06.020","article-title":"Orexinergic signaling mediates light-induced neuronal activation in the dorsal raphe nucleus","volume":"220","author":"Adidharma","year":"2012","journal-title":"Neuroscience"},{"key":"10.1016\/j.drudis.2014.01.001_bib0210","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1111\/j.1742-4658.2006.05322.x","article-title":"Melatonin\u2014nature's most versatile biological signal?","volume":"273","author":"Pandi-Perumal","year":"2006","journal-title":"FEBS J."},{"key":"10.1016\/j.drudis.2014.01.001_bib0215","first-page":"194","article-title":"Melatonin in aging and disease\u2014multiple consequences of reduced secretion, options and limits of treatment","volume":"3","author":"Hardeland","year":"2012","journal-title":"Aging Dis."},{"key":"10.1016\/j.drudis.2014.01.001_bib0220","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.smrv.2004.04.003","article-title":"Melatonin as a hypnotic: pro","volume":"9","author":"Zhdanova","year":"2005","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0225","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0163-7258(95)02020-9","article-title":"Chronobiotics\u2014drugs that shift rhythms","volume":"69","author":"Dawson","year":"1996","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.drudis.2014.01.001_bib0230","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.jsmc.2010.08.001","article-title":"Therapeutics for circadian rhythm sleep disorders","volume":"5","author":"Dodson","year":"2010","journal-title":"Sleep Med. Clin."},{"key":"10.1016\/j.drudis.2014.01.001_bib0235","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev-pharmtox-010510-100528","article-title":"Orexin receptors: pharmacology and therapeutic opportunities","volume":"51","author":"Scammell","year":"2011","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0240","doi-asserted-by":"crossref","first-page":"914168","DOI":"10.5402\/2012\/914168","article-title":"Clinical pharmacology in sleep medicine","volume":"2012","author":"Proctor","year":"2012","journal-title":"ISRN Pharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0245","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1111\/j.1360-0443.2011.03563.x","article-title":"Benzodiazepines revisited\u2014will we ever learn?","volume":"106","author":"Lader","year":"2011","journal-title":"Addiction"},{"key":"10.1016\/j.drudis.2014.01.001_bib0250","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1177\/0269881109106927","article-title":"Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics","volume":"24","author":"Nutt","year":"2010","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0255","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1177\/1756285612454692","article-title":"Diagnosis and management of central hypersomnias","volume":"5","author":"Sonka","year":"2012","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"10.1016\/j.drudis.2014.01.001_bib0260","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S1474-4422(13)70178-9","article-title":"A need for new treatments in narcolepsy","volume":"12","author":"Ferini Strambi","year":"2013","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0265","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.yfrne.2007.08.001","article-title":"Orexin neuronal circuitry: role in the regulation of sleep and wakefulness","volume":"29","author":"Ohno","year":"2008","journal-title":"Front. Neuroendocrinol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0270","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2008.05.060","article-title":"Role of orexin input in the diurnal rhythm of locus coeruleus impulse activity","volume":"1224","author":"Gompf","year":"2008","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2014.01.001_bib0275","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1093\/sleep\/29.11.1439","article-title":"Narcolepsy without cataplexy: 2 subtypes based on CSF hypocretin-1\/orexin-A findings","volume":"29","author":"Oka","year":"2006","journal-title":"Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0280","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.5665\/sleep.2080","article-title":"Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy","volume":"35","author":"Andlauer","year":"2012","journal-title":"Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0285","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1073\/pnas.0400590101","article-title":"Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice","volume":"101","author":"Mieda","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.drudis.2014.01.001_bib0290","doi-asserted-by":"crossref","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":"10.1016\/j.drudis.2014.01.001_bib0295","doi-asserted-by":"crossref","first-page":"e39131","DOI":"10.1371\/journal.pone.0039131","article-title":"Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone","volume":"7","author":"Morairty","year":"2012","journal-title":"PLoS ONE"},{"key":"10.1016\/j.drudis.2014.01.001_bib0300","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nm1544","article-title":"Promotion of sleep by targeting the orexin system in rats, dogs and humans","volume":"13","author":"Brisbare-Roch","year":"2007","journal-title":"Nat. Med."},{"key":"10.1016\/j.drudis.2014.01.001_bib0305","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/clpt.2011.370","article-title":"Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial","volume":"91","author":"Hoever","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.drudis.2014.01.001_bib0310","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1212\/WNL.0b013e31827688ee","article-title":"Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant","volume":"79","author":"Herring","year":"2012","journal-title":"Neurology"},{"key":"10.1016\/j.drudis.2014.01.001_bib0315","first-page":"259","article-title":"Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men","volume":"36","author":"Sun","year":"2013","journal-title":"Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0320","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.5665\/sleep.1996","article-title":"The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia","volume":"35","author":"Bettica","year":"2012","journal-title":"Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0325","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1177\/0269881111408954","article-title":"Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist","volume":"26","author":"Bettica","year":"2012","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0330","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nm0507-525","article-title":"Reply to \u2018Promotion of sleep by targeting the orexin system in rats, dogs and humans\u2019","volume":"13","author":"Tafti","year":"2007","journal-title":"Nat. Med."},{"key":"10.1016\/j.drudis.2014.01.001_bib0335","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.5665\/sleep.2232","article-title":"The dual orexin receptor antagonist almorexan induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors","volume":"35","author":"Mang","year":"2012","journal-title":"Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0340","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5665\/sleep.2442","article-title":"Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy","volume":"36","author":"Black","year":"2013","journal-title":"Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0345","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1017\/S1461145712001083","article-title":"Expression of \u03b11-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT2A receptors","volume":"16","author":"Santana","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0350","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2147\/NSS.S6849","article-title":"Role of 5-HT2A receptor antagonists in the treatment of insomnia","volume":"2","author":"Vanover","year":"2010","journal-title":"Nat. Sci. Sleep"},{"key":"10.1016\/j.drudis.2014.01.001_bib0355","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4103\/0975-3583.85261","article-title":"Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients","volume":"2","author":"Fares","year":"2011","journal-title":"J. Cardiovasc. Dis. Res."},{"key":"10.1016\/j.drudis.2014.01.001_bib0360","doi-asserted-by":"crossref","first-page":"e6968","DOI":"10.1136\/bmj.e6968","article-title":"Treatment of sleep disorders with melatonin","volume":"345","author":"Lerchl","year":"2012","journal-title":"BMJ"},{"key":"10.1016\/j.drudis.2014.01.001_bib0365","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1755-5949.2008.00066.x","article-title":"Pharmacology of ramelteon, a selective MT1\/MT2 receptor agonist: a novel therapeutic drug for sleep disorders","volume":"15","author":"Miyamoto","year":"2009","journal-title":"CNS Neurosci. Ther."},{"key":"10.1016\/j.drudis.2014.01.001_bib0370","doi-asserted-by":"crossref","first-page":"180","DOI":"10.2174\/187152712800269740","article-title":"Melatonergic drugs for therapeutic use in insomnia and sleep disturbances of mood disorders","volume":"11","author":"Srinivasan","year":"2012","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"10.1016\/j.drudis.2014.01.001_bib0375","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.smrv.2010.06.004","article-title":"Histamine in the regulation of wakefulness","volume":"15","author":"Thakkar","year":"2011","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.drudis.2014.01.001_bib0380","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1124\/jpet.110.170134","article-title":"Histamine H3 receptors and sleep\u2013wake regulation","volume":"336","author":"Lin","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.drudis.2014.01.001_bib0385","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.brainres.2003.08.044","article-title":"Wake-related activity of tubermammillary neurons in rats","volume":"992","author":"Ko","year":"2003","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2014.01.001_bib0390","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35048583","article-title":"High constitutive activity of native H3 receptors regulates histamine neurons in brain","volume":"408","author":"Morisset","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2014.01.001_bib0395","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.bcp.2007.01.002","article-title":"The brain H3 receptor as a novel therapeutic target for vigilance and sleep\u2013wake disorders","volume":"73","author":"Parmentier","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0400","doi-asserted-by":"crossref","first-page":"4687","DOI":"10.1073\/pnas.0600451103","article-title":"Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in H1 receptor knockout mice","volume":"103","author":"Huang","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.drudis.2014.01.001_bib0405","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/jpet.110.166876","article-title":"Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease","volume":"336","author":"Brioni","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.drudis.2014.01.001_bib0410","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1017\/S1461145712001411","article-title":"AZD5213: a novel histamine H3 receptor antagonist permitting high daytime and low nocturnal H3 receptor occupancy, a PET study in human subjects","volume":"16","author":"Jucaite","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0415","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/j.1476-5381.2011.01286.x","article-title":"The histamine H3 receptor: from discovery to clinical trials with pitolisant","volume":"163","author":"Schwartz","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0420","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S1474-4422(13)70225-4","article-title":"Pitolisant versus plaebo or modafinil in patients with narcolepsy: a double-blind, randomised trial","volume":"12","author":"Dauvilliers","year":"2013","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.drudis.2014.01.001_bib0425","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.drudis.2009.02.011","article-title":"The histamine H3 receptor as a therapeutic target for CNS disorders","volume":"14","author":"Gemkow","year":"2009","journal-title":"Drug Discov. Today"}],"container-title":["Drug Discovery Today"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644614000026?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644614000026?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:18:12Z","timestamp":1761221892000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1359644614000026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":85,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["S1359644614000026"],"URL":"https:\/\/doi.org\/10.1016\/j.drudis.2014.01.001","relation":{},"ISSN":["1359-6446"],"issn-type":[{"value":"1359-6446","type":"print"}],"subject":[],"published":{"date-parts":[[2014,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Selective targets for arousal-modifying drugs: implications for the treatment of sleep disorders","name":"articletitle","label":"Article Title"},{"value":"Drug Discovery Today","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.drudis.2014.01.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}