Orexin receptors as therapeutic drug targets

Progress in Brain Research

Volumn 198, Issue , 2012, Pages 163-188

  Gotter, Anthony L ^a   Roecker, Anthony J ^a   Hargreaves, Richard ^a   Coleman, Paul J ^a   Winrow, Christopher J ^a   Renger, John J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Agonist; Antagonist; Drug addiction; Feeding; Hypocretin; Insomnia; Neuropeptide; Orexin; Sleep; Vigilance state

Indexed keywords

1 (2 METHYL 6 BENZOXAZOLYL) 3 (1,5 NAPHTHYRIDIN 4 YL)UREA; 1 (6,8 DIFLUORO 2 METHYL 4 QUINOLINYL) 3 (4 DIMETHYLAMINOPHENYL)UREA; ALMOREXANT; DORA 1; DORA 12; DORA 22; ESZOPICLONE; GSK 1059865; JNJ 1037049; MK 6096; OBPT 9; OREXIN 1 RECEPTOR; OREXIN 2 RECEPTOR; OREXIN A; OREXIN B; RECEPTOR BLOCKING AGENT; SB 649868; SB 674042; SUVOREXANT; UNCLASSIFIED DRUG; ZALEPLON; ZOLPIDEM; ZOPICLONE;

ANXIETY DISORDER; AROUSAL; ARTICLE; DRUG DEPENDENCE; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; FEEDING; GENE MUTATION; GENETIC MODEL; HUMAN; INSOMNIA; INTRACELLULAR SIGNALING; METABOLIC SYNDROME X; MOOD DISORDER; NOCICEPTION; NONHUMAN; NONREM SLEEP; POLYSOMNOGRAPHY; PRIORITY JOURNAL; PROTEIN FUNCTION; REM SLEEP;

EID: 84863880593     PISSN: 00796123     EISSN: 18757855     Source Type: Book Series    
DOI: 10.1016/B978-0-444-59489-1.00010-0     Document Type: Chapter

References (150)

1. Adamantidis A.R., Zhang F., Aravanis A.M., Deisseroth K., de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 2007, 450:420-424.
2. Aissaoui H., Koberstein R., Zumbrunn C., Gatfield J., Brisbare-Roch C., Jenck F., et al. N-Glycine-sulfonamides as potent dual orexin 1/orexin 2 receptor antagonists. Bioorganic and Medicinal Chemistry Letters 2008, 18:5729-5733.
3. Arrigoni E., Mochizuki T., Scammell T.E. Activation of the basal forebrain by the orexin/hypocretin neurones. Acta Physiologica (Oxford) 2010, 198:223-235.
4. Asahi S., Egashira S.I., Matsuda M., Iwaasa H., Kanatani A., Ohkubo M., et al. Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B. Bioorganic and Medicinal Chemistry Letters 2003, 13:111-113.
5. Ashton H. Guidelines for the rational use of benzodiazepines. When and what to use. Drugs 1994, 48:25-40.
6. Bartsch T., Levy M.J., Knight Y.E., Goadsby P.J. Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain 2004, 109:367-378.
7. Bergman J.M., Roecker A.J., Mercer S.P., Bednar R.A., Reiss D.R., Ransom R.W., et al. Proline bis-amides as potent dual orexin receptor antagonists. Bioorganic and Medicinal Chemistry Letters 2008, 18:1425-1430.
8. Bettica P., Nucci G., Pyke C., Squassante L., Zamuner S., Ratti E., et al. Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. Journal of Psychopharmacology 2011, http://dx.doi.org/10.1177/0269881111408954.
9. Bingham S., Davey P.T., Babbs A.J., Irving E.A., Sammons M.J., Wyles M., et al. Orexin-A, an hypothalamic peptide with analgesic properties. Pain 2001, 92:81-90.
10. Borgland S.L., Taha S.A., Sarti F., Fields H.L., Bonci A. Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 2006, 49:589-601.
11. Bourgin P., Huitron-Resendiz S., Spier A.D., Fabre V., Morte B., Criado J.R., et al. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. The Journal of Neuroscience 2000, 20:7760-7765.
12. Boutrel B., Kenny P.J., Specio S.E., Martin-Fardon R., Markou A., Koob G.F., et al. Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proceedings of the National Academy of Sciences of the United States of America 2005, 102:19168-19173.
13. Brisbare-Roch C., Clozel M., Jenck F. Effects of repeated oral administration of the orexin receptor antagonist almorexant in male rats and dogs. Sleep 2008, 31:A38.
14. Brisbare-Roch C., Dingemanse J., Koberstein R., Hoever P., Aissaoui H., Flores S., et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nature Medicine 2007, 13:150-155.
15. Burdakov D., Alexopoulos H. Metabolic state signalling through central hypocretin/orexin neurons. Journal of Cellular and Molecular Medicine 2005, 9:795-803.
16. Carter M.E., Adamantidis A., Ohtsu H., Deisseroth K., de Lecea L. Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. The Journal of Neuroscience 2009, 29:10939-10949.
17. Cason A.M., Smith R.J., Tahsili-Fahadan P., Moorman D.E., Sartor G.C., Aston-Jones G. Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity. Physiology and Behavior 2010, 100:419-428.
18. Chemelli R.M., Willie J.T., Sinton C.M., Elmquist J.K., Scammell T., Lee C., et al. Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 1999, 98:437-451.
19. Chen L., McKenna J.T., Bolortuya Y., Winston S., Thakkar M.M., Basheer R., et al. Knockdown of orexin type 1 receptor in rat locus coeruleus increases REM sleep during the dark period. The European Journal of Neuroscience 2010, 32:1528-1536.
20. Cheng J.K., Chou R.C.C., Hwang L.L., Chiou L.C. Antiallodynic effects of intrathecal orexins in a rat model of postoperative pain. The Journal of Pharmacology and Experimental Therapeutics 2003, 307:1065-1071.
21. Coleman P.J., Cox C.D., Roecker A.J. Discovery of dual orexin receptor antagonists (DORAs) for the treatment of insomnia. Current Topics in Medicinal Chemistry 2011, 11:696-725.
22. Coleman P.J., Renger J.J. Orexin receptor antagonists: A review of promising compounds patented since 2006. Expert Opinion on Therapeutic Patents 2010, 20:307-324.
23. Coleman P.J., Schreier J.D., Cox C.D., Breslin M.J., Whitman D.B., McGaughey G.B., et al. Discovery of MK-6096: A novel dual orexin receptor antagonist for the treatment of insomnia 2011, 193.
24. Costa E., Guidotti A. Molecular mechanisms in the receptor action of benzodiazepines. Annual Review of Pharmacology and Toxicology 1979, 19:531-545.
25. Cox C.D., Breslin M.J., Whitman D.B., Schreier J.D., McGaughey G.B., Bogusky M.J., 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-methy l-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia. Journal of Medicinal Chemistry 2010, 53:5320-5332.
26. Cox C.D., McGaughey G.B., Bogusky M.J., Whitman D.B., Ball R.G., Winrow C.J., et al. Conformational analysis of N, N-disubstituted-1,4-diazepane orexin receptor antagonists and implications for receptor binding. Bioorganic and Medicinal Chemistry Letters 2009, 19:2997-3001.
27. De la Herran-Arita A.K., Guerra-Crespo M., Drucker-Colin R. Narcolepsy and orexins: An example of progress in sleep research. Frontiers in Neurology 2011, 2:1-8.
28. de Lecea L., Kilduff T.S., Peyron C., Gao X.B., Foye P.E., Danielson P.E., et al. The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences of the United States of America 1998, 95:322-327.
29. Deadwyler S.A., Porrino L., Siegel J.M., Hampson R.E. Systemic and nasal delivery of orexin-A (hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. The Journal of Neuroscience 2007, 27:14239-14247.
30. Di Fabio R., Pellacani A., Faedo S., Roth A., Piccoli L., Gerrard P., et al. Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders. Bioorganic and Medicinal Chemistry Letters 2011, 21:5562-5567.
31. Dingemanse J., Dorffner G., Hajak G., Benes H., Danker-Hopfe H., Polo O., et al. Proof-of-concept study in primary insomnia patients with ACT-078573, a dual orexin receptor antagonist. Sleep and Biological Rhythms 2007, 5(Suppl):A194.
32. Diniz Behn C.G., Klerman E.B., Mochizuki T., Lin S.C., Scammell T.E. Abnormal sleep/wake dynamics in orexin knockout mice. Sleep 2010, 33:297-306.
33. Dugovic C., Shelton J.E., Aluisio L.E., Fraser I.C., Jiang X.H., Sutton S.W., et al. Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. The Journal of Pharmacology and Experimental Therapeutics 2009, 330:142-151.
34. Dugovic C., Shelton J., Sutton S., Yun S., Li X., Dvorak C., et al. Sleep-inducing effects mediated by selective blockade of orexin OX2 receptors during the light phase in the rat. Sleep 2008, 31:A33.
35. Edwards C.M., Abusnana S., Sunter D., Murphy K.G., Ghatei M.A., Bloom S.R. The effect of the orexins on food intake: Comparison with neuropeptide Y, melanin-concentrating hormone and galanin. The Journal of Endocrinology 1999, 160:R7-R12.
36. Espana R.A., Plahn S., Berridge C.W. Circadian-dependent and circadian-independent behavioral actions of hypocretin/orexin. Brain Research 2002, 943:224-236.
37. Espana R.A., Scammell T.E. Sleep neurobiology from a clinical perspective. Sleep 2011, 34:845-858.
38. Fadel J., Deutch A.Y. Anatomical substrates of orexin-dopamine interactions: Lateral hypothalamic projections to the ventral tegmental area. Neuroscience 2002, 111:379-387.
39. Fortuyn H.A.D., Lappenschaar M.A., Furer J.W., Hodiamont P.P., Rijnders C.A.T., Renier W.O., et al. Anxiety and mood disorders in narcolepsy: A case-control study. General Hospital Psychiatry 2010, 32:49-56.
40. Fujiki N., Yoshida Y., Ripley B., Mignot E., Nishino S. Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog. Sleep 2003, 26:953-959.
41. Fujimoto T., Kunitomo J., Tomata Y., Nishiyama K., Nakashima M., Hirozane M., et al. Discovery of potent, selective, orally active benzoxazepine-based Orexin-2 receptor antagonists. Bioorganic and Medicinal Chemistry Letters 2011, 21:6414-6416.
42. Funato H., Tsai A.L., Willie J.T., Kisanuki Y., Williams S.C., Sakurai T., et al. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metabolism 2009, 9:64-76.
43. Georgescu D., Zachariou V., Barrot M., Mieda M., Willie J.T., Eisch A.J., et al. Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. The Journal of Neuroscience 2003, 23:3106-3111.
44. Gotter A.L., Webber A.L., Coleman P.J., Renger J.J., Winrow C.J. International union of pharmacology: Orexin receptor function, nomenclature and pharmacology. Pharmacological Reviews 2012, (in press), http://dx.doi.org/10.1124/pr.111.005546.
45. Gozzi A., Turrini G., Piccoli L., Massagrande M., Amantini D., Antolini M., et al. Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists. PloS One 2011, 6:e16406.
46. Hagan J.J., Leslie R.A., Patel S., Evans M.L., Wattam T.A., Holmes S., et al. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proceedings of the National Academy of Sciences of the United States of America 1999, 96:10911-10916.
47. Hara J., Beuckmann C.T., Nambu T., Willie J.T., Chemelli R.M., Sinton C.M., et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 2001, 30:345-354.
48. Hara J., Yanagisawa M., Sakurai T. Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions. Neuroscience Letters 2005, 380:239-242.
49. Harris G.C., Aston-Jones G. Arousal and reward: A dichotomy in orexin function. Trends in Neurosciences 2006, 29:571-577.
50. Harris G.C., Wimmer M., Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature 2005, 437:556-559.
51. Haynes A.C., Jackson B., Chapman H., Tadayyon M., Johns A., Porter R.A., et al. A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regulatory Peptides 2000, 96:45-51.
52. Herring W.J., Budd K.S., Hutzelmann J., Snyder E., Snavely D., Liu K., et al. Efficacy and tolerability of the dual orexin receptor antagonist MK-4305 in patients with primary insomnia: Randomized, controlled, adaptive crossover polysomnography study 2010, A0591.
53. Hirose M., Egashira S., Goto Y., Hashihayata T., Ohtake N., Iwaasa H., et al. N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: The first orexin-2 receptor selective non-peptidic antagonist. Bioorganic and Medicinal Chemistry Letters 2003, 13:4497-4499.
54. Hoever P., de Haas S., Chiossi E., van Gerven J., Dingemanse J. Multiple-dose pharmacokinetics, pharmacodynamics, safety, and tolerability of the orexin receptor antagonist almorexant in healthy subjects. Sleep 2008, 31:A38.
55. Holland P.R., Akerman S., Goadsby P.J. Orexin 1 receptor activation attenuates neurogenic dural vasodilation in an animal model of trigeminovascular nociception. The Journal of Pharmacology and Experimental Therapeutics 2005, 315:1380-1385.
56. Holland P.R., Akerman S., Goadsby P.J. Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. The European Journal of Neuroscience 2006, 24:2825-2833.
57. Holmqvist T., Akerman K.E., Kukkonen J.P. Orexin signaling in recombinant neuron-like cells. FEBS Letters 2002, 526:11-14.
58. Holmqvist T., Johansson L., Ostman M., Ammoun S., Akerman K.E., Kukkonen J.P. OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms. The Journal of Biological Chemistry 2005, 280:6570-6579.
59. Honda Y., Doi Y., Ninomiya R., Ninomiya C. Increased frequency of non-insulin-dependent diabetes mellitus among narcoleptic patients. Sleep 1986, 9:254-259.
60. Hoque R., Chesson A.L. Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: Fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem. Journal of Clinical Sleep Medicine 2009, 5:471-476.
61. Ishii Y., Blundell J.E., Halford J.C., Upton N., Porter R., Johns A., et al. Satiety enhancement by selective orexin-1 receptor antagonist SB-334867: Influence of test context and profile comparison with CCK-8S. Behavioural Brain Research 2005, 160:11-24.
62. Ito N., Yabe T., Gamo Y., Nagai T., Oikawa T., Yamada H., et al. I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation. Neuroscience 2008, 157:720-732.
63. Jenck F., Fischer C., Qiu C., Hess P., Kolberstein R., Brisbare-Roch C. Somnolence induced by pharmacological blockade of both orexin OX1 and OX2 receptors in dogs. Sleep and Biological Rhythms 2007, 5(Suppl.):A79. [The 5th Congress of the World Federation of Sleep Research and Sleep Medicine Societies, Cairns, Australia; PO271].
64. Jeong Y., Holden J.E. The role of spinal orexin-1 receptors in posterior hypothalamic modulation of neuropathic pain. Neuroscience 2009, 159:1414-1421.
65. Johnson P.L., Truitt W., Fitz S.D., Minick P.E., Dietrich A., Sanghani S., et al. A key role for orexin in panic anxiety. Nature Medicine 2010, 16:U111-U149.
66. Kajiyama S., Kawamoto M., Shiraishi S., Gaus S., Matsunaga A., Suyama H., et al. Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally-administered orexins in diabetic neuropathic pain model rats. Brain Research 2005, 1044:76-86.
67. Kantor S., Mochizuki T., Janisiewicz A.M., Clark E., Nishino S., Scammell T.E. Orexin neurons are necessary for the circadian control of REM sleep. Sleep 2009, 32:1127-1134.
68. Karteris E., Randeva H.S., Grammatopoulos D.K., Jaffe R.B., Hillhouse E.W. Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals. The Journal of Clinical Endocrinology and Metabolism 2001, 86:4512-4519.
69. Kolberstein R., Aissaoui H., Bur D., Clozel M., Fischli W., Jenck F., et al. Tetrahydroisoquinolines as orexin receptor antagonists: Strategies for lead optimization by solution-phase chemistry. Chimia 2003, 57:270-275.
70. 2+ channels. Neuroreport 2001, 12:2017-2020.
71. Lancel M. Role of GABAA receptors in the regulation of sleep: Initial sleep responses to peripherally administered modulators and agonists. Sleep 1999, 22:33-42.
72. Langmead C.J., Jerman J.C., Brough S.J., Scott C., Porter R.A., Herdon H.J. Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. British Journal of Pharmacology 2004, 141:340-346.
73. 2+ entry: Evidence for involvement of trpc channels and protein kinase C regulation. The Journal of Biological Chemistry 2005, 280:1771-1781.
74. Lee J., Reddy M.M., Kodadek T. Discovery of an orexin receptor positive potentiator. Chemical Science 2010, 1:48-54.
75. Li Y.H., Li S., Wei C.G., Wang H.Y., Sui N., Kirouac G.J. Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats. Psychopharmacology 2010, 212:251-265.
76. Li A.H., Nattie E. Antagonism of rat orexin receptors by almorexant attenuates central chemoreception in wakefulness in the active period of the diurnal cycle. Journal of Physiology-London 2010, 588:2935-2944.
77. Lin L., Faraco J., Li R., Kadotani H., Rogers W., Lin X.Y., et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999, 98:365-376.
78. Lin J.S., Sakai K., Jouvet M. Evidence for histaminergic arousal mechanisms in the hypothalamus of cat. Neuropharmacology 1988, 27:111-122.
79. Liu R.J., van den Pol A.N., Aghajanian G.K. Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. The Journal of Neuroscience 2002, 22:9453-9464.
80. Louhivuori L.M., Jansson L., Nordstrom T., Bart G., Nasman J., Akerman K.E. Selective interference with TRPC3/6 channels disrupts OX1 receptor signalling via NCX and reveals a distinct calcium influx pathway. Cell Calcium 2010, 48:114-123.
81. 2+ influx pathway necessary for coupling to phospholipase C. The Journal of Biological Chemistry 2000, 275:30806-30812.
82. Lutter M., Krishnan V., Russo S.J., Jung S., McClung C.A., Nestler E.J. Orexin signaling mediates the antidepressant-like effect of calorie restriction. The Journal of Neuroscience 2008, 28:3071-3075.
83. Malherbe P., Borroni E., Gobbi L., Knust H., Nettekoven M., Pinard E., et al. Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor. British Journal of Pharmacology 2009, 156:1326-1341.
84. Malherbe P., Roche O., Marcuz A., Kratzeisen C., Wettstein J.G., Bissantz C. Mapping the binding pocket of dual antagonist almorexant to human orexin 1 and orexin 2 receptors: Comparison with the selective OX1 antagonist SB-674042 and the selective OX2 antagonist N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin- 3-ylmethyl-acetamide (EMPA). Molecular Pharmacology 2010, 78:81-93.
85. Marcus J.N., Aschkenasi C.J., Lee C.E., Chemelli R.M., Saper C.B., Yanagisawa M., et al. Differential expression of orexin receptors 1 and 2 in the rat brain. The Journal of Comparative Neurology 2001, 435:6-25.
86. McAtee L.C., Sutton S.W., Rudolph D.A., Li X., Aluisio L.E., Phuong V.K., et al. Novel substituted 4-phenyl-[1,3]dioxanes: Potent and selective orexin receptor 2 (OX(2)R) antagonists. Bioorganic and Medicinal Chemistry Letters 2004, 14:4225-4229.
87. Mieda M., Willie J.T., Hara J., Sinton C.M., Sakurai T., Yanagisawa M. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:4649-4654.
88. Mobarakeh J.I., Takahashi K., Sakurada S., Nishino S., Watanabe H., Kato M., et al. Enhanced antinociception by intracerebroventricularly and intrathecally-administered orexin A and B (hypocretin-1 and-2) in mice. Peptides 2005, 26:767-777.
89. Mochizuki T., Crocker A., McCormack S., Yanagisawa M., Sakurai T., Scammell T.E. Behavioral state instability in orexin knock-out mice. The Journal of Neuroscience 2004, 24:6291-6300.
90. Mochizuki T., Scammell T.E. Orexin/hypocretin: Wired for wakefulness. Current Biology 2003, 13:R563-R564.
91. Monti J.M., Pellejero T., Jantos H. Effects of H1- and H2-histamine receptor agonists and antagonists on sleep and wakefulness in the rat. Journal of Neural Transmission 1986, 66:1-11.
92. Moriguchi T., Sakurai T., Nambu T., Yanagisawa M., Goto K. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neuroscience Letters 1999, 264:101-104.
93. 2+ entry via diacylglycerol-activated channels in differentiated neuroblastoma cells. The Journal of Neuroscience 2006, 26:10658-10666.
94. Nishino S. Hypocretins: Integrators of physiological functions 2005, 39. Springer, New York. L. de Lecea, G. Sutcliffe (Eds.).
95. Nishino S., Ripley B., Overeem S., Lammers G.J., Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000, 355:39-40.
96. Nutt D.J., Stahl S.M. Searching for perfect sleep: The continuing evolution of GABAA receptor modulators as hypnotics. Journal of Psychopharmacology 2010, 24:1601-1612.
97. Ohno K., Sakurai T. Orexin neuronal circuitry: Role in the regulation of sleep and wakefulness. Frontiers in Neuroendocrinology 2008, 29:70-87.
98. Ozcan M., Ayar A., Serhatlioglu I., Alcin E., Sahin Z., Kelestimur H. Orexins activates protein kinase C-mediated Ca(2+) signaling in isolated rat primary sensory neurons. Physiological Research 2010, 59:255-262.
99. Peyron C., Faraco J., Rogers W., Ripley B., Overeem S., Charnay Y., et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nature Medicine 2000, 6:991-997.
100. Piper D.C., Upton N., Smith M.I., Hunter A.J. The novel brain neuropeptide, orexin-A, modulates the sleep-wake cycle of rats. The European Journal of Neuroscience 2000, 12:726-730.
101. Porter R.A., Chan W.N., Coulton S., Johns A., Hadley M.S., Widdowson K., et al. 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor. Bioorganic and Medicinal Chemistry Letters 2001, 11:1907-1910.
102. Rainero I., Gallone S., Valfre W., Ferrero M., Angilella G., Rivoiro C., et al. A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache. Neurology 2004, 63:1286-1288.
103. Rainero I., Rubino E., Gallone S., Fenoglio P., Picci L.R., Giobbe L., et al. Evidence for an association between migraine and the hypocretin receptor 1 gene. The Journal of Headache and Pain 2011, 12:193-199.
104. Renzulli C., Nash M., Wright M., Thomas S., Zamuner S., Pellegatti M., et al. Disposition and metabolism of [14C]SB-649868, an orexin 1 and 2 receptor antagonist, in humans. Drug Metabolism and Disposition 2011, 39:215-227.
105. Rodgers R.J., Halford J.C., Nunes de Souza R.L., Canto de Souza A.L., Piper D.C., Arch J.R., et al. SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats. The European Journal of Neuroscience 2001, 13:1444-1452.
106. Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M., Tanaka H., et al. Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998, 92:573-585.
107. Sakurai T., Mieda M., Masashi Y. Hypocretins: Integrators of physiological functions 2005, 27. Springer, New York. L. de Lecea, G. Sutcliffe (Eds.).
108. Saper C.B., Fuller P.M., Pedersen N.P., Lu J., Scammell T.E. Sleep state switching. Neuron 2010, 68:1023-1042.
109. Saper C.B., Scammell T.E., Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 2005, 437:1257-1263.
110. Scammell T.E., Willie J.T., Guilleminault C., Siegel J.M. A consensus definition of cataplexy in mouse models of narcolepsy. Sleep 2009, 32:111-116.
111. Scammell T.E., Winrow C.J. Orexin receptors: Pharmacology and therapeutic opportunities. Annual Review of Pharmacology and Toxicology 2011, 51:243-266.
112. Schuld A., Blum W.F., Pollmacher T. Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy. Annals of Neurology 2002, 51:660-661.
113. Schuld A., Hebebrand J., Geller F., Pollmacher T. Increased body-mass index in patients with narcolepsy. Lancet 2000, 355:1274-1275.
114. Schurks M., Kurth T., Geissler I., Tessmann G., Diener H.C., Rosskopf D. Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene. Neurology 2006, 66:1917-1919.
115. Schurks M., Limmroth V., Geissler I., Tessmann G., Savidou I., Engelbergs J., et al. Association between migraine and the G1246A polymorphism in the hypocretin receptor 2 gene. Headache 2007, 47:1195-1199.
116. Scott M.M., Marcus J.N., Pettersen A., Birnbaum S.G., Mochizuki T., Scammell T.E., et al. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behavioural Brain Research 2011, 222:289-294.
117. Sharf R., Sarhan M., DiLeone R.J. Role of orexin/hypocretin in dependence and addiction. Brain Research 2010, 1314:130-138.
118. Shoblock J.R., Welty N., Aluisio L., Fraser I., Motley S.T., Morton K., et al. Selective blockade of the orexin-2 receptor attenuates ethanol self-administration, place preference, and reinstatement. Psychopharmacology 2011, 215:191-203.
119. Smart D., Jerman J.C., Brough S.J., Neville W.A., Jewitt F., Porter R.A. The hypocretins are weak agonists at recombinant human orexin-1 and orexin-2 receptors. British Journal of Pharmacology 2000, 129:1289-1291.
120. Smart D., Sabido-David C., Brough S.J., Jewitt F., Johns A., Porter R.A., et al. SB-334867-A: The first selective orexin-1 receptor antagonist. British Journal of Pharmacology 2001, 132:1179-1182.
121. Smith R.J., Tahsili-Fahadan P., Aston-Jones G. Orexin/hypocretin is necessary for context-driven cocaine-seeking. Neuropharmacology 2010, 58:179-184.
122. Strawn J.R., Pyne-Geithman G.J., Ekhator N.N., Horn P.S., Uhde T.W., Shutter L.A., et al. Low cerebrospinal fluid and plasma orexin-A (hypocretin-1) concentrations in combat-related posttraumatic stress disorder. Psychoneuroendocrinology 2010, 35:1001-1007.
123. Sullivan S.S., Guilleminault C. Emerging drugs for insomnia: New frontiers for old and novel targets. Expert Opinion on Emerging Drugs 2009, 14:411-422.
124. Suzuki M., Beuckmann C.T., Shikata K., Ogura H., Sawai T. Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like behavior. Brain Research 2005, 1044:116-121.
125. Taheri S., Sunter D., Dakin C., Moyes S., Seal L., Gardiner J., et al. Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system. Neuroscience Letters 2000, 279:109-112.
126. Tan K.R., Rudolph U., Luscher C. Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends in Neurosciences 2011, 34:188-197.
127. Thannickal T.C., Siegel J.M., Nienhuis R., Moore R.Y. Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy. Brain Pathology 2003, 13:340-351.
128. Trivedi P., Yu H., MacNeil D.J., Van der Ploeg L.H.T., Guan X.M. Distribution of orexin receptor mRNA in the rat brain. FEBS Letters 1998, 438:71-75.
129. 2+ signaling in dopamine neurons of the ventral tegmental area. Neuroreport 2001, 12:1885-1889.
130. van den Pol A.N., Gao X.B., Obrietan K., Kilduff T.S., Belousov A.B. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. The Journal of Neuroscience 1998, 18:7962-7971.
131. van den Pol A.N., Patrylo P.R., Ghosh P.K., Gao X.B. Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin). The Journal of Comparative Neurology 2001, 433:349-363.
132. Watanabe S., Kuwaki T., Yanagisawa M., Fukuda Y., Shimoyama M. Persistent pain and stress activate pain-inhibitory orexin pathways. Neuroreport 2005, 16:5-8.
133. Whitman D.B., Cox C.D., Breslin M.J., Brashear K.M., Schreier J.D., Bogusky M.J., et al. Discovery of a potent, CNS-penetrant orexin receptor antagonist based on an n, n-disubstituted-1,4-diazepane scaffold that promotes sleep in rats. ChemMedChem 2009, 4:1069-1074.
134. Williams K.S., Behn C.G. Dynamic interactions between orexin and dynorphin may delay onset of functional orexin effects: A modeling study. Journal of Biological Rhythms 2011, 26:171-181.
135. Willie J.T., Chemelli R.M., Sinston C.M., Tokita H., Williams S.C., Kisanuki Y.Y., 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, 38:715-730.
136. Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annual Review of Neuroscience 2001, 24:429-458.
137. Winrow C.J., Gotter A.L., Cox C.D., Doran S.M., Tannenbaum P.L., Breslin M.J., et al. Pharmacological characterization of MK-6096-A dual orexin receptor antagonist for insomnia. Neuropharmacology 2012, 62:978-987.
138. Winrow C.J., Gotter A.L., Cox C.D., Doran S.M., Tannenbaum P.L., Breslin M.J., et al. Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist. Journal of Neurogenetics 2011, 25:52-61.
139. Wong K.K., Ng S.Y., Lee L.T., Ng H.K., Chow B.K. Orexins and their receptors from fish to mammals: A comparative approach. General and Comparative Endocrinology 2011, 171:124-130.
140. Xie X.M., Wisor J.P., Hara J., Crowder T.L., LeWinter R., Khroyan T.V., et al. Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. The Journal of Clinical Investigation 2008, 118:2471-2481.
141. Yamamoto T., Nozaki-Taguchi N., Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test in the rat hot plate test. British Journal of Pharmacology 2002, 137:170-176.
142. Yamamoto T., Saito O., Shono K., Aoe T., Chiba T. Anti-mechanical allodynic effect of intrathecal and intracerebroventricular injection of orexin-A in the rat neuropathic pain model. Neuroscience Letters 2003, 347:183-186.
143. Yamamoto T., Saito O., Shono K., Hirasawa S. Activation of spinal orexin-1 receptor produces anti-allodynic effect in the rat carrageenan test. European Journal of Pharmacology 2003, 481:175-180.
144. Yamanaka A., Beuckmann C.T., Willie J.T., Hara J., Tsujino N., Mieda M., et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 2003, 38:701-713.
145. Yamanaka A., Tsujino N., Funahashi H., Honda K., Guan J.L., Wang Q.P., et al. Orexins activate histaminergic neurons via the orexin 2 receptor. Biochemical and Biophysical Research Communications 2002, 290:1237-1245.
146. Yan J.A., Ge L., Huang W., Song B., Chen X.W., Yu Z.P. Orexin affects dorsal root ganglion neurons: A mechanism for regulating the spinal nociceptive processing. Physiological Research 2008, 57:797-800.
147. Yanagisawa, M. (2010), US 2010/0150840 A1, 19 pp.
148. Zeitzer J.M., Buckmaster C.L., Parker K.J., Hauck C.M., Lyons D.M., Mignot E. Circadian and homeostatic regulation of hypocretin in a primate model: Implications for the consolidation of wakefulness. The Journal of Neuroscience 2003, 23:3555-3560.
149. Zhang S., Lin L., Kaur S., Thankachan S., Blanco-Centurion C., Yanagisawa M., et al. The development of hypocretin (orexin) deficiency in hypocretin/ataxin-3 transgenic rats. Neuroscience 2007, 148:34-43.
150. Zhu Y., Miwa Y., Yamanaka A., Yada T., Shibahara M., Abe Y., et al. Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. Journal of Pharmacological Sciences 2003, 92:259-266.