Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX 2 receptor

British Journal of Pharmacology

Volumn 156, Issue 8, 2009, Pages 1326-1341

  Malherbe, P ^a   Borroni, E ^a   Gobbi, L ^a   Knust, H ^a   Nettekoven, M ^a   Pinard, E ^a   Roche, O ^a   Rogers Evans, M ^a   Wettstein, J G ^a   Moreau, J L ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Autoradiography; Binding kinetics; EMPA; Ex vivo receptor occupancy; Inositol phosphate accumulation; Orexin; Orexin B induced hyperlocomotion; OX 2 antagonist; Rat brain distribution; Schild analysis

Indexed keywords

1 (2 METHYL 6 BENZOXAZOLYL) 3 (1,5 NAPHTHYRIDIN 4 YL)UREA; ALMOREXANT; G PROTEIN COUPLED RECEPTOR; INOSITOL PHOSPHATE; N ETHYL 2 [(6 METHOXYPYRIDIN 3 YL)(TOLUENE 2 SULFONYL)AMINO] N PYRIDIN 3 YL METHYLACETAMIDE; OREXIN 2 RECEPTOR; OREXIN 2 RECEPTOR ANTAGONIST; OREXIN A; OREXIN B; OREXIN B [11 ALANINE,15 LEUCINE]; SB 674042; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTORADIOGRAPHY; BINDING AFFINITY; BINDING KINETICS; BRAIN REGION; COMPETITIVE INHIBITION; CONTROLLED STUDY; DOSE RESPONSE; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; IN VIVO STUDY; LOCOMOTION; MALE; MAMMILLARY BODY; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RAT; ROTAROD TEST; SCHILD ANALYSIS; SLEEP WAKING CYCLE; TISSUE DISTRIBUTION;

ADMINISTRATION, ORAL; AMINOPYRIDINES; ANIMALS; AUTORADIOGRAPHY; BEHAVIOR, ANIMAL; BINDING SITES; BINDING, COMPETITIVE; BRAIN; CALCIUM SIGNALING; CELL MEMBRANE; CHO CELLS; CRICETINAE; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INJECTIONS, INTRAPERITONEAL; INOSITOL PHOSPHATES; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; KINETICS; MALE; MICE; MOTOR ACTIVITY; NEUROPEPTIDES; RADIOLIGAND ASSAY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROPEPTIDE; SULFONAMIDES; TRANSFECTION;

EID: 67649890888     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00127.x     Document Type: Article

References (48)

1. Alexander SPH, Mathie A, Peters JA (2008). Guide to receptors and channels (GRAC), 3rd edn. Br J Pharmacol 153 (Suppl. 2 S1 S209.
2. Asahi S, Egashira S, Matsuda M, Iwaasa H, Kanatani A, Ohkubo M et al. (2003). Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B. Bioorg Med Chem Lett 13 : 111 113.
3. Baldo BA, Daniel RA, Berridge CW, Kelley AE (2003). Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464 : 220 237.
4. Bayer L, Serafin M, Eggermann E, Saint-Mleux B, Machard D, Jones BE et al. (2004). Exclusive postsynaptic action of hypocretin-orexin on sublayer 6b cortical neurons. J Neurosci 24 : 6760 6764.
5. Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S et al. (2007). Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 13 : 150 155. (Pubitemid 46245769)
6. Chang H, Saito T, Ohiwa N, Tateoka M, Deocaris CC, Fujikawa T et al. (2007). Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats. Neurosci Res 57 : 462 466.
7. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C et al. (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98 : 437 451.
8. Cluderay JE, Harrison DC, Hervieu GJ (2002). Protein distribution of the orexin-2 receptor in the rat central nervous system. Regul Pept 104 : 131 144.
9. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE et al. (1998). The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95 : 322 327.
10. Desarnaud F, Murillo-Rodriguez E, Lin L, Xu M, Gerashchenko D, Shiromani SN et al. (2004). The diurnal rhythm of hypocretin in young and old F344 rats. Sleep 27 : 851 856.
11. Harris GC, Wimmer M, Aston-Jones G (2005). A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437 : 556 559.
12. Heinonen MV, Purhonen AK, Makela KA, Herzig KH (2008). Functions of orexins in peripheral tissues. Acta Physiol (Oxf) 192 : 471 485.
13. Hirose M, Egashira S, Goto Y, Hashihayata T, Ohtake N, Iwaasa H et al. (2003). N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: the first orexin-2 receptor selective non-peptidic antagonist. Bioorg Med Chem Lett 13 : 4497 4499.
14. Holland P, Goadsby PJ (2007). The hypothalamic orexinergic system: pain and primary headaches. Headache 47 : 951 962.
15. Huang ZL, Qu WM, Li WD, Mochizuki T, Eguchi N, Watanabe T et al. (2001). Arousal effect of orexin A depends on activation of the histaminergic system. Proc Natl Acad Sci USA 98 : 9965 9970.
16. Ida T, Nakahara K, Murakami T, Hanada R, Nakazato M, Murakami N (2000). Possible involvement of orexin in the stress reaction in rats. Biochem Biophys Res Commun 270 : 318 323.
17. Krout KE, Mettenleiter TC, Loewy AD (2003). Single CNS neurons link both central motor and cardiosympathetic systems: a double-virus tracing study. Neuroscience 118 : 853 866.
18. Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ (2004). Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br J Pharmacol 141 : 340 346.
19. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X et al. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98 : 365 376.
20. Lu XY, Bagnol D, Burke S, Akil H, Watson SJ (2000). Differential distribution and regulation of OX1 and OX2 orexin/hypocretin receptor messenger RNA in the brain upon fasting. Horm Behav 37 : 335 344.
21. Malherbe P, Kratochwil N, Muhlemann A, Zenner MT, Fischer C, Stahl M et al. (2006). Comparison of the binding pockets of two chemically unrelated allosteric antagonists of the mGlu5 receptor and identification of crucial residues involved in the inverse agonism of MPEP. J Neurochem 98 : 601 615.
22. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M et al. (2001). Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 435 : 6 25.
23. Nakamura T, Uramura K, Nambu T, Yada T, Goto K, Yanagisawa M et al. (2000). Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic system. Brain Res 873 : 181 187.
24. Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K (1999). Distribution of orexin neurons in the adult rat brain. Brain Res 827 : 243 260.
25. Nishino S (2007). The hypocretin/orexin receptor: therapeutic prospective in sleep disorders. Expert Opin Investig Drugs 16 : 1785 1797.
26. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000). Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355 : 39 40.
27. Ohno K, Sakurai T (2008). Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol 29 : 70 87.
28. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y et al. (2000). A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6 : 991 997.
29. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG et al. (1998). Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18 : 9996 10015.
30. Piper DC, Upton N, Smith MI, Hunter AJ (2000). The novel brain neuropeptide, orexin-A, modulates the sleep-wake cycle of rats. Eur J Neurosci 12 : 726 730.
31. Rainero I, Gallone S, Rubino E, Ponzo P, Valfre W, Binello E et al. (2008). Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache. Headache 48 : 1108 1114. Epub 2008 Apr 8.
32. Rainero I, Rubino E, Valfre W, Gallone S, De Martino P, Zampella E et al. (2007). Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis. J Headache Pain 8 : 152 156.
33. Sakamoto F, Yamada S, Ueta Y (2004). Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: possible involvement of central orexins on stress-activated central CRF neurons. Regul Pept 118 : 183 191.
34. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H et al. (1998). Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92 : 573 585.
35. Scammell TE, Saper CB (2005). Orexin, drugs and motivated behaviors. Nat Neurosci 8 : 1286 1288.
36. Sharf R, Sarhan M, Dileone RJ (2008). Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell. Biol Psychiatry 64 : 175 183.
37. Siegel JM (2004). Hypocretin (orexin): role in normal behavior and neuropathology. Annu Rev Psychol 55 : 125 148.
38. Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA et al. (2001). SB-334867-A: the first selective orexin-1 receptor antagonist. Br J Pharmacol 132 : 1179 1182.
39. Taheri S, Sunter D, Dakin C, Moyes S, Seal L, Gardiner J et al. (2000). Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system. Neurosci Lett 279 : 109 112.
40. Tang J, Chen J, Ramanjaneya M, Punn A, Conner AC, Randeva HS (2008). The signalling profile of recombinant human orexin-2 receptor. Cell Signal 20 : 1651 1661.
41. Thorpe AJ, Kotz CM (2005). Orexin A in the nucleus accumbens stimulates feeding and locomotor activity. Brain Res 1050 : 156 162.
42. Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM (1998). Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438 : 71 75.
43. Voisin T, Rouet-Benzineb P, Reuter N, Laburthe M (2003). Orexins and their receptors: structural aspects and role in peripheral tissues. Cell Mol Life Sci 60 : 72 87.
44. Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY et al. (2003). Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: molecular genetic dissection of non-REM and REM sleep regulatory processes. Neuron 38 : 715 730.
45. Winsky-Sommerer R, Boutrel B, de Lecea L (2005). Stress and arousal: the corticotrophin-releasing factor/hypocretin circuitry. Mol Neurobiol 32 : 285 294.
46. Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T et al. (2004). Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci 24 : 11439 11448.
47. Yamanaka A, Tsujino N, Funahashi H, Honda K, Guan JL, Wang QP et al. (2002). Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem Biophys Res Commun 290 : 1237 1245.
48. Yoshida Y, Fujiki N, Nakajima T, Ripley B, Matsumura H, Yoneda H et al. (2001). Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur J Neurosci 14 : 1075 1081.