Drugs to Interfere with Orexins (Hypocretins)

Drug News and Perspectives

Volumn 16, Issue 10, 2003, Pages 669-681

  Selbach, Oliver ^a   Eriksson, Krister S ^a   Haas, Helmut L ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

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; 4 AMINOBUTYRIC ACID; 4 HYDROXYBUTYRIC ACID; AMPHETAMINE DERIVATIVE; CAFFEINE; CALCIUM ION; DYNORPHIN; G PROTEIN COUPLED RECEPTOR; GLUCAGON; GLUTAMIC ACID; HORMONE RECEPTOR STIMULATING AGENT; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; MELANIN CONCENTRATING HORMONE; MODAFINIL; NEUROPEPTIDE RECEPTOR; OREXIN; OREXIN A; OREXIN B; OREXIN RECEPTOR; OREXIN RECEPTOR AGONIST; OREXIN RECEPTOR ANTAGONIST; PEPTIDE HORMONE ANTAGONIST; PHOSPHOLIPASE C; PROTEIN KINASE; SB 284422; SB 668875; SECRETIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASOACTIVE INTESTINAL POLYPEPTIDE;

APPETITE; AROUSAL; BEHAVIOR; CATAPLEXY; CIRCADIAN RHYTHM; DRUG TARGETING; EATING DISORDER; HOMEOSTASIS; HUMAN; MEMORY DISORDER; MOOD DISORDER; NARCOLEPSY; NEUROENDOCRINE DISEASE; NEUROPSYCHIATRY; NONHUMAN; PAIN; PEPTIDERGIC NERVOUS SYSTEM; REVIEW; SLEEP DISORDER; STRESS;

ANIMALS; CARRIER PROTEINS; CATAPLEXY; CENTRAL NERVOUS SYSTEM STIMULANTS; CIRCADIAN RHYTHM; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; NARCOLEPSY; NEUROPEPTIDES; NEUROTRANSMITTER AGENTS; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROPEPTIDE;

EID: 1042301999     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2003.16.10.829298     Document Type: Review

References (203)

1. de Lecea, L. et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 1998, 95: 322-7.
2. Sakurai, T. 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.
3. Nishino, S. and Mignot, E. Pharmacological aspects of human and canine narcolepsy. Prog Neurobiol 1997, 52: 27-78.
4. Scammell, T.E. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol 2003, 53: 154-66.
5. Siegel, J.M. Narcolepsy: A key role for hypocretins (orexins). Cell 1999, 98: 409-12.
6. Taheri, S., Zeitzer, J.M. and Mignot, E. The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu Rev Neurosci 2002, 25: 283-313.
7. Mignot, E., Taheri, S. and Nishino, S. Sleeping with the hypothalamus: Emerging therapeutic targets for sleep disorders. Nat Neurosci 2002, 5(Suppl 1): 1071-5.
8. Willie, J.T., Chemelli, R.M., Sinton, C.M. and Yanagisawa, M. To eat or to sleep? Orexin in the regulation of feeding and wakefidness. Annu Rev Neurosci 2001, 24: 429-58.
9. Sutcliffe, J.G. and de Lecea, L. The hypocretins: Setting the arousal threshold. Nat Rev Neurosci 2002, 3: 339-49.
10. Kilduff, T.S. and Peyron, C. The hypocretin/orexin ligand-receptor system: Implications for sleep and sleep disorders. Trends Neurosci 2000, 23: 359-65.
11. Saper, C.B., Chou, T.C. and Scammell, T.E. The sleep switch: Hypothalamic control of sleep and wakefulness. Trends Neurosci 2001, 24: 726-31.
12. Kukkonen, J.P., Holmqvist, T., Ammoun, S. and Akerman, K.E. Functions of the orexinergic/hypocretinergic system. Am J Physiol Cell Physiol 2002, 283: C1567-91.
13. Kirchgessner, A.L. Orexins in the brain-gut axis. Endocr Rev 2002, 23: 1-15.
14. Cai, X.J. et al. Orexins and feeding: Special occasions or everyday occurrence? Regul Pept 2002, 104: 1-9.
15. Smart, D. and Jerman, J. The physiology and pharmacology of the orexins. Pharmacol Ther 2002, 94: 51-61.
16. Rodgers, R.J., Ishii, Y., Halford, J.C. and Blundell, J.E. Orexins and appetite regulation. Neuropeptides 2002, 36: 303-25.
17. Dun, N.J. et al. Orexins: A role in medullary sympathetic outflow. Regul Pept 2000, 96: 65-70.
18. Shirasaka, T., Takasaki, M. and Kannan, H. Cardiovascular effects of leptin and orexins. Am J Physiol Regul Integr Comp Physiol 2003, 284: R639-51.
19. Taylor, M.M. and Samson, W.K. The other side of the orexins: Endocrine and metabolic actions. Am J Physiol Endocrinol Metab 2003, 284: E13-7.
20. Sakurai, T. Orexin: A link between energy homeostasis and adaptive behaviour. Curr Opin Clin Nutr Metab Care 2003, 6: 353-60.
21. Li, Y., Gao, X.B., Sakurai, T. and Van Den Pol, A.N. Hypocretin/orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system. Neuron 2002, 36: 1169-81.
22. Eggermann, E. et al. The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarizarion. J Neurosci 2003, 23: 1557-62.
23. Yamanaka, A., Muraki, Y., Tsujino, N., Goto, K. and Sakurai, T. Regulation of orexin neurons by the monoaminergic and cholinergic systems. Biochem Biophys Res Commun 2003, 303: 120-9.
24. Yamanaka, A. et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 2003, 38: 701-13.
25. Bernardis, L.L. and Bellinger, L.L. The lateral hypothalamic area revisited: Ingestive behavior. Neurosci Biobehav Rev 1996, 20: 189-287.
26. Kayaba, Y. et al. Attenuated defense response and low basal blood pressure in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol 2003, 285: R581-93.
27. Peyron, C. et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998, 18: 9996-10015.
28. Date, Y. et al. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci USA 1999, 96: 748-53.
29. Nambu, T. et al. Distribution of orexin neurons in the adult rat brain. Brain Res 1999, 827: 243-60.
30. Marcus, J.N. et al. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 2001, 435: 6-25.
31. Trivedi, P., Yu, H., MacNeil, D.J., Van der Ploeg, L.H. and Guan, X.M. Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 1998, 438: 71-5.
32. Johren, O., Neidert, S.J., Kummer, M., Dendorfer, A. and Dominiak, P. Preproorexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology 2001, 142: 3324-31.
33. Willie, J.T. 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.
34. Mazzocchi, G., Malendowicz, L.K., Gottardo, L., Aragona, F. and Nussdorfer, G.G. Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade. J Clin Endocrinol Metab 2001, 86: 778-82.
35. Karteris, E., Randeva, H.S., Grammatopoulos, D.K., Jaffe, R.B. and Hillhouse, E.W. Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals. J Clin Endocrinol Metab 2001, 86: 4512-9.
36. Randeva, H.S., Karteris, E., Grammatopoulos, D. and Hillhouse, E.W. Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: Implications for adrenal function and energy homeostasis. J Clin Endocrinol Metab 2001, 86, 4808-13.
37. van den Top, M. et al. Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones. J Physiol 2003, 549: 809-21.
38. Craig, A.D. How do you feel? Interoception: The sense of the physiological condition of the body. Nat Rev Neurosci 2002, 3: 655-66.
39. Saper, C.B. The central autonomic nervous system: Conscious visceral perception and autonomic pattern generation. Annu Rev Neurosci 2002, 25: 433-69.
40. Pacak, K. and Palkovits, M. Stressor specificity of central neuroendocrine responses: Implications for stress-related disorders. Endocr Rev 2001, 22: 502-48.
41. Krout, K.E., Mettenleiter, T.C. and Loewy, A.D. Single CNS neurons link both central motor and cardiosympathetic systems: A double-virus tracing study. Neuroscience 2003, 118: 853-66.
42. Ciriello, J., Rosas-Arellano, M.P., Solano-Flores, L.P. and De Oliveira, C.V. Identification of neurons containing orexin-B (hypocretin-2) immunoreactivity in limbic structures. Brain Res 2003, 967: 123-31.
43. Samson, W.K. and Taylor, M.M. Hypocretin/orexin suppresses corticotroph responsiveness in vitro. Am J Physiol Regul Integr Comp Physiol 2001, 281: R1140-5.
44. Russell, S.H. et al. The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats. J Neuroendocrinol 2001, 13: 561-6.
45. Al Barazanji, K.A., Wilson, S., Baker, J., Jessop, D.S. and Harbuz, M.S. Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats. J Neuroendocrinol 2001, 13: 421-4.
46. Kuru, M. et al. Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 2000, 11: 1977-80.
47. Ida, T. et al. Both corticotropin releasing factor and neuropeptide Y are involved in the effect of orexin (hypocretin) on the food intake in rats. Neurosci Lett 2000, 293: 119-22.
48. Ida, T. et al. Possible involvement of orexin in the stress reaction in rats. Biochem Biophys Res Commun 2000, 270: 318-23.
49. Jaszberenyi, M., Bujdoso, E., Pataki, I. and Telegdy, G. Effects of orexins on the hypothalamic-pituitary-adrenal system. J Neuroendocrinol 2000, 12: 1174-8.
50. Stricker-Krongrad, A. and Beck, B. Modulation of hypothalamic hypocretin/orexin mRNA expression by glucocorticoids. Biochem Biophys Res Commun 2002, 296: 129-33.
51. Szekely, M., Petervari, E., Balasko, M., Hernadi, I. and Uzsoki, B. Effects of orexins on energy balance and thermoregulation. Regul Pept 2002, 104: 47-53.
52. Haynes, A.C. et al. Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. Regul Pept 2002, 104: 153-9.
53. Monda, M., Viggiano, A. and De Luca, V. Haloperidol reduces the sympathetic and thermogenic activation induced by orexin A. Neurosci Res 2003, 45: 17-23.
54. Monda, M., Viggiano, A., Mondola, P. and De, L., V. Inhibition of prostaglandin synthesis reduces hyperthermic reactions induced by hypoeretin-1/orexin A. Brain Res 2001, 909: 68-74.
55. Gulia, K.K., Mallick, H.N. and Kumar, V.M. Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats. Neuroscience 2003, 116: 921-3.
56. Campbell, R.E., Grove, K.L. and Smith, M.S. Gonadotropin-releasing hormone neurons coexpress orexin 1 receptor immunoreactivity and receive direct contacts by orexin fibers. Endocrinology 2003, 144: 1542-8.
57. Grudt, T.J., Van Den Pol, A.N. and Perl, E.R. Hypocretin-2 (orexin-B) modulation of superficial dorsal horn activity in rat. J Physiol 2002, 538: 517-25.
58. Van Den Pol, A.N. Hypothalomic hypocretin (orexin): Robust innervation of the spinal cord. J Neurosci 1999, 19: 3171-82.
59. Bingham, S. et al. Orexin-A, an hypothalamic peptide with analgesic properties. Pain 2001, 92: 81-90.
60. Zhu, L., Onaka, T., Sakurai, T. and Yada, T. Activation of orexin neurones after noxious but not conditioned fear stimuli in rats. Neuroreport 2002, 13: 1351-3.
61. Jaeger, L., Farr, S., Banks, W. and Morley, J. Effects of orexin-A on memory processing. Peptides 2002, 23: 1683.
62. Telegdy, G. and Adamik, A. The action of orexin A on passive avoidance learning. Involvement of transmitters. Regul Pept 2002, 104: 105-10.
63. Wu, M. et al. Hypocretin increases impulse flow in the septohippocampal GABAergic pathway: Implications for arousal via a mechanism of hippocampal disinhibition. J Neurosci 2002, 22: 7754-65.
64. Li, X.L. et al. Orexin-A (hypocretin-1) impairs Morris water maze performance and ca1-schaffer collateral long-term potentiation in rats. Neuroscience 2003, 119: 1221-8.
65. Selbach, O., Doreulee, N., Poelchen, W., Eriksson, K.S., Sergeeva, O.A., and Haas, H.L. Orexins/hypocretins mediate theta-related synaptic plasticity in the hippocampus by regulation of sympathetic outflow and integration of coincident signaling. Soc Neurosci Abstr 2002.
66. Switonska, M.M., Kaczmarek, P., Malendowicz, L.K. and Nowak, K.W. Orexins and adipoinsular axis function in the rat. Regul Pept 2002, 104: 69-73.
67. Ouedraogo, R., Naslund, E. and Kirchgessner, A.L. Glucose regulates the release of orexin-A from the endocrine pancreas. Diabetes 2003, 52: 111-7.
68. Kelley, A.E. and Berridge, K.C. The neuroscience of natural rewards: Relevance to addictive drugs. J Neurosci 2002, 22: 3306-11.
69. Saper, C.B., Chou, T.C. and Elmquist, J.K. The need to feed: Homeostatic and hedonic control of eating. Neuron 2002, 36: 199-211.
70. Zeitzer, J.M. et al. Circadian and homeostatic regulation of hypocretin in a primate model: Implications for the consolidation of wakefulness. J Neurosci 2003, 23: 3555-60.
71. Estabrooke, I.V. et al. Fos expression in orexin neurons varies with behavioral state. J Neurosci 2001, 21: 1656-62.
72. Kiyashchenko, L.I. et al. Release of hypocretin (orexin) during waking and sleep states. J Neurosci 2002, 22: 5282-6.
73. Lin, L. et al. Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: The effect of circadian time, age and genetic background. Peptides 2002, 23: 2203-11.
74. Wu, M.F., John, J., Maidment, N., Lam, H.A. and Siegel, J.M. Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement. Am J Physiol Regul Integr Comp Physiol 2002, 283: R1079-86.
75. Espana, R.A., Plahn, S. and Berridge, C.W. Circadian-dependent and circadian-independent behavioral actions of hypocretin/orexin. Brain Res 2002, 943: 224-36.
76. Farkas, B., Vilagi, I. and Detari, L. Effect of orexin-A on discharge rate of rat suprachiasmatic nucleus neurons in vitro. Acta Biol Hung 2002, 53: 435-43.
77. Sakurai, T. et al. Structure and function of human prepro-orexin gene. J Biol Chem 1999, 274: 17771-6.
78. Nilaweera, K.N., Barrett, P., Mercer, J.G. and Morgan, P.J. Precursor-protein convertase 1 gene expression in the mouse hypothalamus: Differential regulation by ob gene mutation, energy deficit and administration of leptin, and coexpression with prepro-orexin. Neuroscience 2003, 119: 713-20.
79. Lund, P.E. et al. The orexin OX1 receptor activates a novel Ca2+ influx pathway necessary for coupling to phospholipase C. J Biol Chem 2000, 275: 30806-12.
80. Holmqvist, T., Akerman, K.E. and Kukkonen, J.P. High specificity of human orexin receptors for orexins over neuropeptide Y and other neuropeptides. Neurosci Lett 2001, 305: 177-80.
81. Sylwia, A.S. et al. Distinct recognition of OX1 and OX2 receptors by orexin peptides. J Pharmacol Exp Ther 2003.
82. Kane, J.K., Tanaka, H., Parker, S.L., Yanagisawa, M. and Li, M.D. Sensitivity of orexin-A binding to phospholipase C inhibitors, neuropeptide Y, and secretin. Biochem Biophys Res Commun 2000, 272: 959-65.
83. Campbell, R.E. et al. Orexin neurons express a functional pancreatic polypeptide Y4 receptor. J Neurosci 2003, 23: 1487-97.
84. Laemmle, B. et al. Characterization of the NPGP receptor and identification of a novel short mRNA isoform in human hypothalamus. Regul Pept 2003, 111: 21-9.
85. Hoang, Q.V., Bajic, D., Yanagisawa, M., Nakajima, S. and Nakajima, Y. Orexin (hypocretin) effects on GIRK channels. J Neurophysiol 2003, 90: 693-702.
86. Brown, R.E., Sergeeva, O.A., Eriksson, K.S. and Haas, H.L. Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J Neurosci 2002, 22: 8850-9.
87. Liu, R.J., Van Den Pol, A.N. and Aghajanian, G.K. Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. J Neurosci 2002, 22: 9453-64.
88. Yang, B. and Ferguson, A.V. Orexin-A depolarizes dissociated rat area postrema neurons through activation of a nonselective cationic conductance. J Neurosci 2002, 22: 6303-8.
89. Yang, B. and Ferguson, A.V. Orexin-A depolarizes nucleus tractus solitarius neurons through effects on nonselective cationic and K+ conductances. J Neurophysiol 2003, 89: 2167-75.
90. Sergeeva, O.A., Korotkova, T.M., Scherer, A., Brown, R.E. and Haas, H.L. Co-expression of non-selective cation channels of the transient receptor potential canonical family in central aminergic nerones. J Neurochem 2003, 85: 1547-52.
91. Eriksson, K.S., Sergeeva, O., Brown, R.E. and Haas, H.L. Orexin/hypocretin excites the histaminergic neurons of the tubero-mammillary nucleus. J Neurosci 2001, 21: 9273-9.
92. Korotkova, T.M., Sergeeva, O.A., Eriksson, K.S., Haas, H.L. and Brown, R.E. Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci 2003, 23: 7-11.
93. Korotkova, T.M., Eriksson, K.S., Haas, H.L. and Brown, R.E. Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro. Regul Pept 2002, 104: 83-9.
94. Evans, N.A. et al. Visualizing differences in ligand-induced beta-arrestin-GFP interactions and trafficking between three recently characterized G protein-coupled receptors. J Neurochem 2001, 77: 476-85.
95. Hilairet, S., Bouaboula, M., Carriere, D., Le Fur, G. and Casellas, P. Hypersensitization of the orexin 1 receptor by the CB1 receptor: Evidence for cross-talk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 2003, 278: 23731-7.
96. Conarello, S.L. et al. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci USA 2003, 100: 6825-30.
97. Maulon-Feraille, L. et al. Appetite-boosting property of pro-melanin-concentrating hormone(131-165) (neuropeptide-glutamic acid-isoleucine) is associated with proteolytic resistance. J Pharmacol Exp Ther 2002, 302: 766-73.
98. Zhu, L. et al. The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: In vivo metabolism of pituitary adenylate cyclase activating polypeptide [1-38]. J Biol Chem 2003, 278: 22418-23.
99. Kastin, A.J. and Akerstrom, V. Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther 1999, 289: 219-23.
100. Caillol, M. et al. Localization of orexins and their receptors in the rat olfactory system: Possible modulation of olfactory perception by a neuropeptide synthesized centrally or locally. Brain Res 2003, 960: 48-61.
101. Born, J. et al. Sniffing neuropeptides: A transnasal approach to the human brain. Nat Neurosci 2002, 5: 514-6.
102. Arihara, Z. et al. Orexin-A in the human brain and tumor tissues of ganglioneuroblastoma and neuroblastoma. Peptides 2000, 21: 565-70.
103. Kummer, M., Neidert, S.J., Johren, O. and Dominiak, P. Orexin (hypocretin) gene expression in rat ependymal cells. Neuroreport 2001, 12: 2117-20.
104. Irving, E.A. et al. Increased cortical expression of the orexin-1 receptor following permanent middle cerebral artery occlusion in the rat. Neurosci Lett 2002, 324: 53-6.
105. Asahi, S. et al. Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B. Bioorg Med Chem Lett 2003, 13: 111-3.
106. Darker, J.G. et al. Structure-activity analysis of truncated orexin-A analogues at the orexin-1 receptor. Bioorg Med Chem Lett 2001, 11: 737-40.
107. Shibahara, M. et al. Structure, tissue distribution, and pharmacological characterization of Xenopus orexins. Peptides 1999, 20: 1169-76.
108. Jones, D.N. et al. Effects of centrally administered orexin-B and orexin-A: A role for orexin-1 receptors in orexin-B-induced hyperactivity. Psychopharmacology 2001, 153: 210-8.
109. Duxon, M.S. et al. Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement. Psychopharmacology 2001, 153: 203-9.
110. Piper, D.C., Upton, N., Smith, M.I. and Hunter, A.J. The novel brain neuropeptide, orexin-A, modulates the sleep-wake cycle of rats. Eur J Neurosci 2000, 12: 726-30.
111. Yamamoto, T., Nozaki-Taguchi, N. and Chiba, T. Analgesic effect of intrathecally, administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol 2002, 137: 170-6.
112. Dahmen, N., Querings, K., Grun, B. and Bierbrauer, J. Increased frequency of migraine in narcoleptic patients. Neurology 1999, 52: 1291-3.
113. Nishino, S. et al. Decreased brain histamine content in hypocretin/ orexin receptor-2 mutated narcoleptic dogs. Neurosci Lett 2001, 313: 125-8.
114. Chemelli, R.M. et al. Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 1999, 98: 437-51.
115. Lin, L. et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999, 98: 365-76.
116. Hara, J. et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 2001, 30: 345-54.
117. Thannickal, T.C. et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000, 27: 469-74.
118. Peyron, C. 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.
119. Hublin, C., Partinen, M., Heinonen, E.H., Puukka, P. and Salmi, T. Selegiline in the treatment of narcolepsy. Neurology 1994, 44: 2095-101.
120. Kiyashchenko, L.I., Mileykovskiy, B.Y., Lai, Y.Y. and Siegel, J.M. Increased and decreased muscle tone with orexin (hypocretin) microinjections in the locus coeruleus and pontine inhibitory area. J Neurophysiol 2001, 85: 2008-16.
121. Mileykovskiy, B.Y., Kiyashchenko, L.I. and Siegel, J.M. Muscle tone facilitation and inhibition after orexin-A (hypocretin-1) microinjections into the medial medulla. J Neurophysiol 2002, 87: 2480-9.
122. Gulyani, S., Wu, M.F., Nienhuis, R., John, J. and Siegel, J.M. Cataplexy-related neurons in the amygdala of the narcoleptic dog. Neuroscience 2002, 112: 355-65.
123. John, J., Wu, M.F., Kodama, T. and Siegel, J.M. Intravenously administered hypocretin-1 alters brain amino acid release: An in vivo microdialysis study in rats. J Physiol 2003, 548: 557-62.
124. Krahn, L.E., Moore, W.R. and Altchuler, S.T. Narcolepsy and obesity: Remission of severe cataplexy with sibutramine. 2001, 2: 63-5.
125. Wisor, J.P. et al. Dopaminergic role in stimulant-induced wakefulness. J Neurosci 2001, 21: 1787-94.
126. Hyman, S.E. and Malenka, R.C. Addiction and the brain: The nearobiology of compulsion and its persistence. Nat Rev Neurosci 2001, 2: 695-703.
127. Lu, J., Chou, T. C. and Saper, C.B. Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray (PAG). Soc Neurosci Abstr 2002.
128. Georgescu, D. et al. Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. J Neurosci 2003, 23: 3106-11.
129. Boutrel, B., Fabre, V., Koob, G. and de Lecea, L. Increased hypocretin levels in rats exposed to a long-term access to cocaine. FENS Forum 2002 (2003).
130. Scammell, T.E. et al. Hypothalamic arousal regions are activated during modafinil-induced wakefidness. J Neurosci 2000, 20: 8620-8.
131. Thakkar, M.M., Winston, S. and McCarley, R.W. Orexin neurons of the hypothalamus express adenosine A1 receptors. Brain Res 2002, 944: 190-4.
132. Mikkelsen, J.D. et al. Hypocretin (orexin) in the rat pineal gland: A central transmitter with effects on norodrenaline-induced release of melatonin. Eur J Neurosci 2001, 14: 419-25.
133. Sergeeva, O.A., Eriksson, K.S., Sharonova, I.N., Vorobjev, V.S. and Haas, H.L. GABA(A) receptor heterogeneity in histaminergic neurons. Eur J Neurosci 2002, 16: 1472-82.
134. Weinshilboum, R.M., Otterness, D.M. and Szumlanski, C.L. Methylation pharmacogenetics: Catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol 1999, 39: 19-52.
135. Tafti, M. and Dauvilliers, Y. Pharmacogenomics in the treatment of narcolepsy. Pharmacogenomics 2003, 4: 23-33.
136. Egan, M.F. et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001, 98: 6917-22.
137. Zubieta, J.K. et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 2003, 299: 1240-3.
138. Fadel, J., Bubser, M. and Deutch, A.Y Differential activation of orexin neurons by antipsychotic drugs associated with weight gain. J Neurosci 2002, 22: 6742-6.
139. Matsuzaki, I. et al. Involvement of the serotonergic system in orexin-induced behavioral alterations in rats. Regul Pept 2002, 104: 119-23.
140. Nakamura, T. et al. Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic system. Brain Res 2000, 873: 181-7.
141. Rush, C.R., Kelly, T.H., Hays, L.R., Baker, R.W. and Wooten, A.F. Acute behavioral and physiological effects of modafinil in drug abusers. Behav Pharmacol 2002, 13: 105-15.
142. Fredholm, B.B., Battig, K., Holmen, J., Nehlig, A. and Zvartau, E.E. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 1999, 51: 83-133.
143. Porkka-Heiskanen, T. et al. Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness. Science 1997, 276: 1265-8.
144. Satoh, S., Matsumura, H., Suzuki, F. and Hayaishi, O. Promotion of sleep mediated by the A2a-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats. Proc Natl Acad Sci USA 1996, 93:, 5980-4.
145. Lindskog, M. et al. Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine. Nature 2002, 418: 774-8.
146. Yao, L. et al. betagamma Dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signaling and regulate ethanol consumption. Cell 2002, 109: 733-43.
147. Svenningsson, P. et al. Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine Prozac). Proc Natl Acad Sci USA 2002, 99: 3182-7.
148. Maitre, M. The gamma-hydroxybutyrate signalling system in brain: Organization and functional implications. Prog Neurobiol 1997, 51: 337-61.
149. Bernasconi, R., Mathivet, P., Bischoff, S. and Marescaux, C. Gamma-hydroxybutyric acid: An endogenous neuromodulator with abuse potential? Trends Pharmacol Sci 1999, 20: 135-41.
150. Hogema, B.M. et al. Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase. Nat Genet 2001, 29: 212-6.
151. Nelson, L.E. et al. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003, 98: 428-36.
152. Nelson, L.E. et al. The sedative component of anesthesia is mediated by GABA(A) receptors in an endogenous sleep pathway. Nat Neurosci 2002, 5: 979-84.
153. Stevens, D.R., Kuramasu, A. and Haas, H.L. GABAB-receptor-mediated control of GABAergic inhibition in rat histaminergic neurons in vitro. Eur J Neurosci 1999, 11: 1148-54.
154. Eriksson, K.S., Sergeeva, O., Selbach, O. and Haas, H.L. Orexin/hypocretin neurons control GABAergic inputs to the tubero-mamillary neurons. J Neurosci 2003 (submitted).
155. Hagan, J.J. et al. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci USA 1999, 96: 10911-6.
156. Horvath, T.L. et al. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J Comp Neurol 1999, 415: 145-59.
157. Burlet, S., Tyler, C.J. and Leonard, C.S. Direct and indirect excitation of late rodorsal tegmental neurons by hypocretin/orexin peptides: Implications for wakefulness and narcolepsy. J Neurosci 2002, 22: 2862-72.
158. Eggermann, E. et al. Orexins/hypocretins excite basal forebrain cholinergic neurones. Neuroscience 2001, 108: 177-81.
159. Belousov, A.B., O'Hara, B.F. and Denisova, J.V. Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation. J Neurosci 2001, 21: 2015-27.
160. Gutierrez, A. et al. Effects of fluoxetine administration on neuropeptide Y and orexins in obese Zucker rat hypothalamus. Obes Res 2002, 10: 532-40.
161. Haas, H. and Panula, P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci 2003, 4: 121-30.
162. Gillard, E.R. et al. The second messenger cAMP elicits eating by an anatomically specific action in the perifornical hypothalamus. J Neurosci 1998, 18: 2646-52.
163. Huang, Z.L. et al. Arousal effect of orexin A depends on activation of the histaminergic system. Proc Natl Acad Sci USA 2001, 98: 9965-70.
164. Inzunza, O., Seron-Ferre, M.J., Bravo, H. and Torrealba, F. Tuberomammillary nucleus activation anticipates feeding under a restricted schedule in rats. Neurosci Lett 2000, 293: 139-42.
165. Parmentier, R. et al. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: Evidence for the tole of brain histamine in behavioral and sleep-wake control. J Neurosci 2002, 22: 7695-711.
166. Mollet, A. et al. Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin. Am J Physiol Regul Integr Comp Physiol 2001, 281: R1442-8.
167. Masaki, T., Yoshimatsu, H., Chiba, S., Watanabe, T. and Sakata, T. Targeted disruption of histamine H1-receptor attenuates regulatory effects of leptin on feeding, adiposity, and UCP family in mice. Diabetes 2001, 50: 385-91.
168. Torrealba, F., Yanagisawa, M. and Saper, C.B. Colocalization of orexin A and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats. Neuroscience 2003, 119: 1033-44.
169. Abrahamson, E.E., Leak, R.K. and Moore, R.Y. The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 2001, 12: 435-40.
170. Van Den Pol, A.N., Gao, X.B., Obrietan, K., Kilduff, T.S. and Belousov, A.B. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. J Neurosci 1998, 18: 7962-71.
171. Hirota, K. et al. Orexin A and B evoke noradrenaline release from rat cerebrocortical slices. Br J Pharmacol 2001, 134: 1461-6.
172. Peever, J.H., Lai, Y.Y. and Siegel, J.M. Excitatory effects of hypocretin-1 (orexin-A) in the trigeminal motor nucleus are reversed by NMDA antagonism. J Neurophysiol 2003, 89: 2591-600.
173. John, J., Wu, M.F., Kodama, T. and Siegel, J.M. Intravenously administered hypocretin-1 alters brain amino acid release: An in vivo microdialysis study in rats. J Physiol 2003, 548: 557-62.
174. Gerashchenko, D., Salin-Pascual, R. and Shiromani, P.J. Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta. Brain Res 2001, 913: 106-15.
175. Martin, G., Fabre, V., Siggins, G.R. and de Lecea, L. Interaction of the hypocretins with neurotransmitters in the nucleus accumbens. Regul Pept 2002, 104: 111-7.
176. Wortley, K.E., Chang, G.Q., Davydova, Z. and Leibowitz, S.F. Peptides that regulate food intake: Orexin gene expression is increased during states of hypertriglyceridemia. Am J Physiol Regul Integr Comp Physiol 2003, 284: R1454-65.
177. Grabauskas, G. and Moises, H.C. Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin. J Physiol 2003, 549: 37-56.
178. Davis, S.F., Williams, K.W., Xu, W., Glatzer, N.R. and Smith, B.N. Selective enhancement of synaptic inhibition by hypocretin (orexin) in rat vagal motor neurons: Implications for autonomic regulation. J Neurosci 2003, 23: 3844-54.
179. Waleh, N.S., Apte-Deshpande, A., Terao, A., Ding, J. and Kilduff, T.S. Modulation of the promoter region of prepro-hypocretin by alpha-interferon. Gene 2001, 262: 123-8.
180. Hakansson, M., de Lecea, L., Sutcliffe, J.G., Yanagisawa, M. and Meister, B. Leptin receptor- and STAT3-immunoreactivities in hypocretin/orexin neurones of the lateral hypothalamus. J Neuroendocrinol 1999, 11: 653-63.
181. Kalra, S.P. et al. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999, 20: 68-100.
182. Van Den Pol, A.N. et al. Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP-expressing locus coeruleus. J Physiol 2002, 541: 169-85.
183. Follwell, M.J. and Ferguson, A.V. Cellular mechanisms of orexin actions on paraventricular nucleus neurones in rat hypothalamus. J Physiol 2002, 545: 855-67.
184. Top, M.M. et al. Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones. J Physiol 2003, 549: 809-21.
185. Shirasaka, T., Kunitake, T., Takasaki, M. and Kannan, H. Neuronal effects of orexins: relevant to sympathetic and cardiovascular functions. Regul Pept 2002, 104: 91-5.
186. Antunes, V.R., Brailoiu, G.C., Kwok, E.H., Scruggs, P. and Dun, N.J. Orexins/hypocretins excite rat sympathetic preganglionic neurons in vivo and in vitro. Am J Physiol Regul Integr Comp Physiol 2001, 281: R1801-7.
187. Johren, O., Bruggemann, N., Dendorfer, A. and Dominiak, P. Gonadal steroids differentially regulate the messenger ribonucleic acid expression of pituitary orexin type 1 receptors and adrenal orexin type 2 receptors. Endocrinology 2003, 144: 1219-25.
188. Griffond, B., Risold, P.Y., Jacquemard, C., Colard, C. and Fellmann, D. Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat lateral hypothalamic area. Neurosci Lett 1999, 262: 77-80.
189. Komaki, G. et al. Orexin-A and leptin change inversely in fasting non-obese subjects. Eur J Endocrinol 2001, 144: 645-51.
190. Borbely, A.A. Sleep in the rat during food deprivation and subsequent restitution of food. Brain Res 1977, 124: 457-71.
191. Pollak, C.P. and Green, J. Eating and its relationships with subjective alertness and sleep in narcoleptic subjects living without temporal cues. Sleep 1990, 13: 467-78.
192. Matarese, G. et al. Balancing susceptibility to infection and autoimmunity: A role for leptin? Trends Immunol 2002, 23: 182-7.
193. Matsuzaki, J., Kuwamura, M., Yamaji, R., Inui, H. and Nakano, Y. Inflammatory responses to lipopolysaccharide are suppressed in 40% energy-restricted mice. J Nutr 2001, 131: 2139-44.
194. Honda, Y., Doi, Y., Ninomiya, R. and Ninomiya, C. Increased frequency of non-insulin-dependent diabetes mellitus among narcoleptic patients. Sleep 1986, 9: 254-9.
195. Schuld, A., Hebebrand, J., Geller, F. and Pollmacher, T. Increased body-mass index in patients with narcolepsy. Lancet 2000, 355: 1274-5.
196. Nishino, S. et al. Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy. Ann Neurol 2001, 50: 381-8.
197. Nestler, E.J. et al. Neurobiology of depression. Neuron 2002, 34: 13-25.
198. Cummings, D.E. and Schwartz, M.W. Genetics and pathophysiology of human obesity. Annu Rev Med 2003, 54: 453-71.
199. Sergeyev, V., Broberger, C., Gorbatyuk, O. and Hokfelt, T. Effect of 2-mercaptoacetate and 2-deoxy-D-glucose administration on the expression of NPY, AGRP, POMC, MCH and hypocretin/orexin in the rat hypothalamus. Neuroreport 2000, 11: 117-21.
200. Toshinai, K. et al. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 2003, 144: 1506-12.
201. Kohno, D., Gao, H.Z., Muroya, S., Kikuyama, S. and Yada, T. Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca(2+) signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 2003, 52: 948-56.
202. Chou, T.C. et al. Orexin (hypocretin) neurons contain dynorphin. J Neurosci 2001, 21: RC168.
203. Clegg, D.J., Air, E.L., Woods, S.C. and Seeley, R.J. Eating elicited by orexin-A, but not melanin-concentrating hormone, is opioid mediated. Endocrinology 2002, 143: 2995-3000.