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2)Partinen M, Kornum BR, Plazzi G, et al. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol. 2014; 13: 600-13
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4)Nagahara T, Saitoh T, Kutsumura N, et al. Design and synthesis of non-peptide, selective orexin receptor 2 agonists. J Med Chem. 2015, 58: 7931-7
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5)Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998; 92: 573-85
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9)Nambu T, Sakurai T, Mizukami K, et al. Distribution of orexin neurons in the adult rat brain. Brain Res. 1999; 827: 243-60
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11)Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007; 8: 171-81
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14)Peyron C, Faraco J, Rogers W, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000; 6: 991-7
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20)Sasaki K, Suzuki M, Mieda M, et al. Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice. PLoS One. 2011; 6: e20360
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21)Tsunematsu T, Kilduff TS, Boyden ES, et al. Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J Neurosci. 2011; 31: 10529-39
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22)Marcus JN, Aschkenasi CJ, Lee CE, et al. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol. 2001; 435: 6-25
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24)Hondo M, Nagai K, Ohno K, et al. Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintenance of basal sleep/wake states. Acta Physiol. 2010; 198: 287-94
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25)Willie JT, Chemelli RM, Sinton CM, et al. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron. 2003; 38: 715-30
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26)Hasegawa E, Yanagisawa M, Sakurai T, et al. Orexin neurons suppress narcolepsy via 2 distinct efferent pathways. J Clin Invest. 2014; 124: 604-16
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27)Hirai N, Nishino S. Recent advances in the treatment of narcolepsy. Curr Treat Options Neurol. 2011; 13: 437-57
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28)Mieda M, Willie JT, Hara J, et al. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci U S A. 2004; 101: 4649-54
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29)Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2011; 51: 243-66
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30)厚生労働科学研究・障害者対策総合研究事業「睡眠薬の適正使用及び減量・中止のための診療ガイドラインに関する研究班」および日本睡眠学会・睡眠薬使用ガイドライン作成ワーキンググループ.睡眠薬の適正な使用と休薬のための診療ガイドライン.2013
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31)Liguori C, Romigi A, Nuccetelli M, et al. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol. 2014; 71: 1498-505
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32)Lucey BP, Holtzman DM. How amyloid, sleep and memory connect. Nat Neurosci. 2015; 18: 933-4
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33)Brisbare-Roch C, Dingemanse J, Koberstein R, et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007; 13: 150-5
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34)Hoever P, de Haas S, Winkler J, et al. Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant. Clin Pharmacol Ther. 2010; 87: 593-600
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35)Cox CD, Breslin MJ, Whitman DB, et al. 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. J Med Chem. 2010; 53: 5320-32
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36)Herring WJ, Snyder E, Budd K, et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012; 79: 2265-74
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37)Sun H, Kennedy WP, Wilbraham D, et al. Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men. Sleep. 2013; 36: 259-67
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38)Michelson D, Snyder E, Paradis E, et al. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014; 13: 461-71
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39)Herring WJ, Connor KM, Ivgy-May N, et al. Suvorexant in Patients with Insomnia: Results from Two 3-Month Randomized Controlled Clinical Trials. Biol Psychiatry. 2014. [Epub ahead of print]
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40)Vermeeren A, Sun H, Vuurman EF, et al. On-the-road driving performance the morning after bedtime use of suvorexant 20 and 40 mg: a study in non-elderly healthy volunteers. Sleep. 2015; 38: 1803-13
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41)Bettica P, Squassante L, Zamuner S, et al. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep. 2012; 35: 1097-104
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42)Bettica P, Squassante L, Groeger JA, et al. Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia. Neuropsychopharmacology. 2012; 37: 1224-33
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43)Gotter AL, Garson SL, Stevens J, et al. Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators. BMC Neurosci. 2014; 15: 109
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44)Ma J, Svetnik V, Snyder E, et al. Electroencephalographic power spectral density profile of the orexin receptor antagonist suvorexant in patients with primary insomnia and healthy subjects. Sleep. 2014; 37: 1609-19
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45)Bonaventure P, Yun S, Johnson PL, et al. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects. J Pharmacol Exp Ther. 2015; 352: 590-601
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46)Dugovic C, Shelton JE, Aluisio LE, et al. Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. J Pharmacol Exp Ther. 2009; 330: 142-51
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47)Dugovic C, Shelton JE, Yun S, et al. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism. Front Neurosci. 2014; 8: 28
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49)Hoyer D, Durst T, Fendt M, et al. Distinct effects of IPSU and suvorexant on mouse sleep architecture. Front Neurosci. 2013; 7: 235
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50)Tabuchi S, Tsunematsu T, Black SW, et al. Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J Neurosci. 2014; 34: 6495-509
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51)Winrow CJ, Renger JJ. Discovery and development of orexin receptor antagonists as therapeutics for insomnia. Br J Pharmacol. 2014; 171: 283-93
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52)内村直尚.オレキシン受容体拮抗薬による不眠症治療の新たなるアプローチ.日本睡眠学会第40回定期学術集会.2015
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53)Coleman PJ, Schreier JD, Cox CD, et al. Discovery of [(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl][5-methyl-2 -(pyrimidin-2-yl)phenyl]methanone (MK-6096): a dual orexin receptor antagonist with potent sleep-promoting properties. ChemMedChem. 2012; 7: 415-24
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54)Yoshida Y, Naoe Y, Terauchi T, et al. Discovery of (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluor opyridin-2-yl)cyclopropanecarboxamide (E2006): A potent and efficacious oral orexin receptor antagonist. J Med Chem. 2015; 58: 4648-64
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55)Letavic MA, Bonaventure P, Carruthers NI, et al. Novel Octahydropyrrolo[3,4-c]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate. J Med Chem. 2015; 58: 5620-36
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