Biological examination of melanin concentrating hormone receptor 1: Multi-tasking from the hypothalamus

Drug News and Perspectives

Volumn 19, Issue 5, 2006, Pages 273-286

  Rokosz, Laura L ^a   Hobbs, Douglas W ^a  

^a PHARMACOPEIA INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMG 076; AMINOPIPERAZINE INDAZOLE DERIVATIVE; ATC 0065; ATC 0175; CORTICOTROPIN; FLUOXETINE; GHRELIN; GW 3430; HORMONE RECEPTOR; INDAZOLE DERIVATIVE; INSULIN; LEPTIN; MELANIN CONCENTRATING HORMONE; MELANIN CONCENTRATING HORMONE RECEPTOR 1; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; MELANIN CONCENTRATING HORMONE RECEPTOR 2; N (6 DIMETHYLAMINOMETHYL 5,6,7,8 TETRAHYDRO 2 NAPHTHYL) 4' FLUORO 1,1' BIPHENYL 4 CARBOXAMIDE; NALOXONE; NBI 1A; NBI 1B; OREXIN; RECEPTOR BLOCKING AGENT; SB 568849; SNAP 7941; SNAP 94847; T 71; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ANXIETY; APPETITE; BINDING AFFINITY; BRAIN; CLINICAL TRIAL; DEPRESSION; DRUG INHIBITION; EMOTION; EXPERIMENTAL MODEL; FEEDING BEHAVIOR; FOOD INTAKE; GENE OVEREXPRESSION; HOMEOSTASIS; HORMONE RECEPTOR INTERACTION; HUMAN; HYPOTHALAMUS; IN VIVO STUDY; INSULIN RESISTANCE; NONHUMAN; NUCLEOTIDE SEQUENCE; OBESITY; PROTEIN EXPRESSION; RECEPTOR BINDING; REVIEW; SATIETY; STRESS; TRANQUILIZING ACTIVITY; WEIGHT GAIN; WEIGHT REDUCTION; WILD TYPE;

AMINO ACID SEQUENCE; ANIMALS; BODY WEIGHT; HUMANS; HYPOTHALAMIC HORMONES; HYPOTHALAMUS; MELANINS; MOLECULAR SEQUENCE DATA; OBESITY; PITUITARY HORMONES; RECEPTORS, SOMATOSTATIN; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 33746880663     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2006.19.5.985938     Document Type: Review

References (108)

1. Kordik, C.P. and Reitz, A.B. Pharmacological treatment of obesity: Therapeutic strategies. J Med Chem 1999, 42: 181-201.
2. Crowley, V.E.F., Yeo, G.S.H. and O'Rahilly, S. Obesity therapy: Altering the energy intake-and-expenditure balance sheet. Nat Rev Drug Discov 2002, 1: 276-86.
3. Hervieu, G. Melanin-concentrating hormone functions in the nervous system: Food intake and stress. Expert Opin Ther Targets 2003, 7: 495-511.
4. Gibson, W.T., Pissios, P., Trombly, D.J. et al. Melanin-concentrating hormone receptor mutations and human obesity: Functional analysis. Obes Res 2004, 12: 743-9.
5. Wermter, A.-K., Reichwald, K., Buech, T. et al. Mutation analysis of the MCHR1 gene in human obesity. Eur J Endocrinol 2005, 152: 851-62.
6. Borowsky, B., Durkin, M.M., Ogozalek, K. et al. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med 2002, 8: 825-30.
7. Chaki, S., Funakoshi, T., Hirota-Okuno, S. et al. Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: Nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists. J Pharmacol Exp Ther 2005, 313: 831-9.
8. Monzon, M.E., de Souza, M.M., Izquierdo, L.A., Izquierdo, I., Barros, D.M. and de Barioglio, S.R. Melanin-concentrating hormone (MCH) modifies memory retention in rats. Peptides 1999, 20: 1517-9.
9. Adamantidis, A., Thomas, E., Foidart, A. et al. Disrupting the melanin-concentrating hormone receptor I in mice leads to cognitive deficits and alterations of NMDA receptor function. Eur J Neurosci 2005, 21: 2837-44.
10. Bohlooly, Y.M., Mahlapuu, M., Andersen, H. et al. Osteoporosis in MCHR1-deficient mice. Biochem Biophys Res Commun 2004, 318: 964-9.
11. Murray, J.F., Adan, R.A.H., Walker, R. et al. Melanin-concentrating hormone, melanocortin receptors and regulation of luteinizing hormone release. J Neuroendocrinol 2000, 12: 217-23.
12. Verlaet, M., Adamantidis, A., Coumans, B. et al. Human immune cells express ppMCH mRNA and functional MCHR1 receptor. FEBS Lett 2002, 527: 205-10.
13. Dyke, H.J. and Ray, N.C. Recent developments in the discovery of MCH-1R antagonists for the treatment of obesity - an update. Expert Opin Ther Patents 2005, 15: 1303-13.
14. Browning, A. Recent developments in the discovery of melanin- concentrating hormone antagonists: Novel antiobesity agents. Expert Opin Ther Patents 2004, 14: 313-25.
15. Carpenter, A.J. and Hertzog, D.L. Melanin-concentrating hormone receptor antagonists as potential antiobesity agents. Expert Opin Ther Patents 2002, 12: 1639-46.
16. McBriar, M.D. and Kowalski, T.J. Melanin-concentrating hormone as a therapeutic target. Ann Rep Med Chem 2005, 40: 119-33.
17. Mashiko, S., Ishihara, A., Gomori, A. et al. Antiobesity effect of a melanin-concentrating hormone 1 receptor antagonist in diet-induced obese mice. Endocrinology 2005, 146: 3080-6.
18. Vasudevan, A., Verzal, M.K., Wodka, D. et al. Identification of aminopiperidine benzamides as MCHr1 antagonists. Bioorg Med Chem Lett 2005, 15: 3412-6.
19. McBriar, M.D., Guzik, H., Xu, R. et al. Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: Orally efficacious antiobesity therapeutics. J Med Chem 2005, 48: 2274-7.
20. Takekawa, S., Asami, A., Ishihara, Y. et al. T-226296: A novel, orally active and selective melanin-concentrating hormone receptor antagonist. Eur J Pharmacol 2002, 438: 129-35.
21. Smith, D.G., Davis, R.J., Rorick-Kehn, L. et al. Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral, and corticolimbic neurochemical stress responses in mice. Neuropsychopharmacology 2006, 31: 1135-45.
22. Kawauchi, H., Kawazoe, I., Tsubokawa, M., Kishida, M. and Baker, B.I. Characterization of melanin-concentrating hormone in chum salmon pituitaries. Nature 1983, 305: 321-3.
23. Nahon, J.L. The melanin-concentrating hormone: From the peptide to the gene. Crit Rev Neurobiol 1994, 8: 221-62.
24. Viale, A., Ortola, C., Vernier, P., Breton, C., Presse, F. and Nahon, J.L. Structure, expression, and evolution of the variant MCH gene in primates. Ann N Y Acad Sci 1998, 839: 214-8.
25. Toumaniantz, G., Bittencourt, J.C. and Nahon, J.L. The rat melanin-concentrating hormone gene encodes an additional putative protein in a different reading frame. Endocrinology 1996, 137: 4518-21.
26. Borsu, L., Presse, F. and Nahon, J.L. The AROM gene, spliced mRNAs encoding new DNA/RNA-binding proteins are transcribed from the opposite strand of the melanin-concentrating hormone gene in mammals. J Biol Chem 2000, 275: 40576-87.
27. Ludwig, D.S., Mountjoy, K.G., Tatro, J.B. et al. Melanin-concentrating hormone: A functional melanocortin antagonist in the hypothalamus. Am J Physiol Cell Physiol 1998, 274: E627-33.
28. Gonzalez, M.I., Kalia, V., Hole, D.R. and Wilson, C.A. alpha-Melanocyte-stimulating hormone (alpha-MSH) and melanin-concentrating hormone (MCH) modify monoaminergic levels in the preoptic area of the rat. Peptides 1997, 18: 387-92.
29. Bachner, D., Kreienkamp, H., Weise, C., Buck, F. and Richter, D. Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1). FEBS Lett 1999, 457: 522-4.
30. Lembo, P.M.C., Grazzini, E., Cao, J. et al. The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor. Nat Cell Biol 1999, 1: 267-71.
31. Saito, Y., Nothacker, H.P., Wang, Z., Lin, S.H., Leslie, F. and Civelli, O. Molecular characterization of the melanin-concentrating-hormone receptor. Nature 1999, 400: 265-9.
32. Chambers, J., Ames, R.S., Bergsma, D. et al. Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature 1999, 400: 261-4.
33. Tan, C.P., Sano, H., Iwaasa, H. et al. Melanin-concentrating hormone receptor subtypes 1 and 2: Species-specific gene expression. Genomics 2002, 79: 785-92.
34. Hawes, B.E., Kil, E., Green, B., O'Neill, K., Fried, S. and Graziano, M.P. The melanin-concentrating hormone receptor couples to multiple G proteins to activate diverse intracellular signaling pathways. Endocrinology 2000, 141: 4524-32.
35. Lakaye, B., M.A., Zorzi, W. and Grisar, T. Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor reveals the presence of an intron in the gene. Biochim Biophys Acta 1998, 1401: 216-20.
36. Rhee, M.H., Nevo, I., Levy, R. and Vogel, Z. Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor. FEBS letters 2000, 466: 300-4.
37. Bachner, D., Kreienkamp, H.-J. and Richter, D. MIZIP, a highly conserved, vertebrate specific melanin-concentrating hormone receptor 1 interacting zinc-finger protein. FEBS Lett 2002, 526: 124-8.
38. Murdoch, H., Feng, G.-J., Bachner, D. et al. Periplakin interferes with G protein activation by the melanin-concentrating hormone receptor-1 by binding to the proximal segment of the receptor C-terminal tail. J Biol Chem 2005, 280: 8208-20.
39. Sailer, A.W., Sano, H., Zeng, Z. et al. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc Natl Acad Sci U S A 2001, 98: 7564-9.
40. Wang, S., Behan, J., O'Neill, K. et al. Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2. J Biol Chem 2001, 276: 34664-70.
41. An, S., Cutler, G., Zhao, J.J. et al. Identification and characterization of a melanin-concentrating hormone receptor. Proc Natl Acad Sci U S A 2001, 98: 7576-81.
42. Hill, J., Duckworth, M., Murdock, P. et al. Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. J Biol Chem 2001, 276: 20125-9.
43. Mori, M., Harada, M., Terao, Y. et al. Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem Biophys Res Commun 2001, 283: 1013-8.
44. Bednarek, M.A., Tan, C., Hreniuk, D.L. et al. Synthesis and biological evaluation in vitro of a selective, high potency peptide agonist of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1. J Biol Chem 2002, 277: 13821-6.
45. Bednarek, M.A., Hreniuk, D.L., Tan, C. et al. Synthesis and biological evaluation in vitro of selective, high affinity peptide antagonists of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1. Biochemistry 2002, 41: 6383-90.
46. Bednarek, M. Preparation of melanin-concentrating hormone analogs active at the MCH-2R and their uses. 2002-US16513 2002097037, 20020528, 2002.
47. Drozdz, R., Siegrist, W., Baker, B.I., Chluba-de Tapia, J. and Eberle, A.N. Melanin-concentrating hormone binding to mouse melanoma cells in vitro. FEBS Lett 1995, 359: 199-202.
48. Mountjoy, K.G. and Wong, J. Obesity, diabetes and functions for proopiomelanocortin-derived peptides. Mol Cell Endocrinol 1997, 128: 171-7.
49. Bittencourt, J.C., Presse, F., Arias, C. et al. The melanin-concentrating hormone system of the rat brain: An immuno- and hybridization histochemical characterization. J Comp Neurol 1992, 319: 218-45.
50. Viale, A., Zhixing, Y., Breton, C. et al. The melanin-concentrating hormone gene in human: Flanking region analysis, fine chromosome mapping, and tissue-specific expression. Brain Res Mol Brain Res 1997, 46: 243-55.
51. Hervieu, G.J., Cluderay, J.E., Harrison, D. et al. The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. Eur J Neurosci 2000, 12: 1194-216.
52. Katsuura, G. and Inui, A. Melanin-concentrating hormone as a metabolic and cognitive regulatory factor. Curr Med Chem: CNS Agents 2003, 3: 217-27.
53. Hoebel, B.G. Feeding: Neural control of intake. Annu Rev Physiol 1971, 33: 533-68.
54. Hervieu, G. and Nahon, J.L. Pro-melanin concentrating hormone messenger ribonucleic acid and peptides expression in peripheral tissues of the rat. Neuroendocrinology 1995, 61: 348-64.
55. Bradley, R.L., Kokkotou, E.G., Maratos-Flier, E. and Cheatham, B. Melanin-concentrating hormone regulates leptin synthesis and secretion in rat adipocytes. Diabetes 2000, 49: 1073-7.
56. Bradley, R.L., Mansfield, J.P.R., Maratos-Flier, E. and Cheatham, B. Melanin-concentrating hormone activates signaling pathways in 3T3-L1 adipocytes. Am J Physiol 2002, 283: E584-92.
57. Anonymous. Br Soc Invest Dermatol Ann Meet (Warwick, 9-11 April) 2001.
58. Br J Dermatol 2001, 144: 651-77.
59. Kemp, E.H., Waterman, E.A., Hawes, B.E. et al. The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo. J Clin Invest 2002, 109: 923-30.
60. Pissios, P. and Maratos-Flier, E. Melanin-concentrating hormone: From fish skin to skinny mammals. Trends Endocrinol Metab 2003, 14: 243-8.
61. Della-Zuana, O., Presse, F., Ortola, C., Duhault, J., Nahon, J.L. and Levens, N. Acute and chronic administration of melanin-concentrating hormone enhances food intake and body weight in Wistar and Sprague-Dawley rats. Int J Obes 2002, 26: 1289-95.
62. Gomori, A., Ishihara, A., Ito, M. et al. Chronic intracerebroventricular infusion of MCH causes obesity in mice. Am J Physiol Cell Physiol 2003, 284: E583-8.
63. Suply, T., Della Zuana, O., Audinot, V. et al. SLC-1 receptor mediates effect of melanin-concentrating hormone on feeding behavior in rat: A structure-activity study. J Pharmacol Exp Ther 2001, 299: 137-46.
64. Ludwig, D.S., Tritos, N.A., Mastaitis, J.W. et al. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 2001, 107: 379-86.
65. Shearman, L.P., Camacho, R.E., Sloan Stribling, D. et al. Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. Eur J Pharmacol 2003, 475: 37-47.
66. Pereira-da-Silva, M., De Souza, C.T., Gasparetti, A.L., Saad, M.J. and Velloso, L.A. Melanin-concentrating hormone induces insulin resistance through a mechanism independent of body weight gain. J Endocrinol 2005, 186: 193-201.
67. Ito, M., Gomori, A., Ishihara, A. et al. Characterization of MCH-mediated obesity in mice. Am J Physiol Cell Physiol 2003, 284: E940-5.
68. Clegg, D.J., Air, E.L., Benoit, S.C., Sakai, R.S., Seeley, R.J. and Woods, S.C. Intraventricular melanin-concentrating hormone stimulates water intake independent of food intake. Am J Physiol Cell Physiol 2003, 284: R494-9.
69. Presse, F. and Nahon, J.L. Differential regulation of melanin-concentrating hormone gene expression in distinct hypothalamic areas under osmotic stimulation in rat. Neuroscience 1993, 55: 709-20.
70. Kennedy, A.R., Todd, J.F., Dhillo, W.S. et al. Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: Further evidence for a stimulatory role in the adrenal axis via SLC-1. J Neuroendocrinol 2003, 15: 268-72.
71. Kennedy, A.R., Todd, J.F., Stanley, S.A. et al. Melanin-concentrating hormone (MCH) suppresses thyroid stimulating hormone (TSH) release, in vivo and in vitro, via the hypothalamus and the pituitary. Endocrinology 2001, 142: 3265-8.
72. Bluet-Pajot, M.T., Presse, F., Voko, Z. et al. Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on stress-induced release of adrenocorticotropin in the rat. J Neuroendocrinol 1995, 7: 297-303.
73. Elliott, J.C., Harrold, J.A., Brodin, P. et al. Increases in melanin-concentrating hormone and MCH receptor levels in the hypothalamus of dietary-obese rats. Brain Res Mol Brain Res 2004, 128: 150-9.
74. Erlanson-Albertsson, C. How palatable food disrupts appetite regulation. Basic Clin Pharmacol Toxicol 2005, 97: 61-73.
75. Shimada, M., Tritos, N.A., Lowell, B.B., Flier, J.S. and Maratos-Flier, E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 1998, 396: 670-4.
76. Zhou, D., Shen, Z., Strack, A.M., Marsh, D.J. and Shearman, L.P. Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice. Regul Pept 2005, 124: 53-63.
77. Segal-Lieberman, G., Bradley, R.L., Kokkotou, E. et al. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc Natl Acad Sci U S A 2003, 100: 10085-90.
78. Marsh, D.J., Weingarth, D.T., Novi, D.E. et al. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A 2002, 99: 3240-5.
79. Gonzalez, M.I., Vaziri, S. and Wilson, C.A. Behavioral effects of alpha-MSH and MCH after central administration in the female rat. Peptides 1996, 17: 171-7.
80. Kokkotou, E., Jeon, J.Y., Wang, X. et al. Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms. Am J Physiol Regul Integr Comp Physiol 2005, 289: R117-24.
81. Yamada, M., Miyakawa, T., Duttaroy, A. et al. Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature 2001, 410: 207-12.
82. Chen, Y., Hu, C., Hsu, C.-K. et al. Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology 2002, 143: 2469-77.
83. Astrand, A., Bohlooly, Y.M., Larsdotter, S. et al. Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity. Am J Physiol 2004, 287: R749-58.
84. Bjursell, M., Egecioglu, E., Gerdin, A.-K. et al. Importance of melanin-concentrating hormone receptor for the acute effects of ghrelin. Biochem Biophys Res Commun 2005, 326: 759-65.
85. Sirek, A., Vranic, M., Sirek, O.V., Vigas, M. and Policova, Z. Effect of growth hormone on acute glucagon and insulin release. Am J Physiol 1979, 237: E107-12.
86. Pierluissi, J., Pierluissi, R. and Ashcroft, S.J. Effects of growth hormone on insulin release in the rat. Diabetologia 1980, 19: 391-6.
87. Murray, J.F., Mercer, J.G., Adan, R.A. et al. The effect of leptin on luteinizing hormone release is exerted in the zona incerta and mediated by melanin-concentrating hormone. J Neuroendocrinol 2000, 12: 1133-9.
88. Qu, D., Ludwig, D.S., Gammeltoft, S. et al. A role for melanin-concentrating hormone in the central regulation of feeding behavior. Nature 1996, 380: 243-7.
89. Sahu, A. Evidence suggesting that galanin (GAL), melanin-concentrating hormone (MCH), neurotensin (NT), proopiomelanocortin (POMC) and neuropeptide Y (NPY) are targets of leptin signaling in the hypothalamus. Endocrinology 1998, 139: 795-8.
90. Sahu, A. Leptin decreases food intake induced by melanin-concentrating hormone (MCH), galanin (GAL) and neuropeptide Y (NPY) in the rat. Endocrinology 1998, 139: 4739-42.
91. Huang, Q., Viale, A., Picard, F., Nahon, J.-L., Richard, D. Effects of leptin on melanin-concentrating hormone expression in the brain of lean and obese Lepob/Lepob mice. Neuroendocrinology 1999, 69: 145-53.
92. Kokkotou, E.G., Tritos, N.A., Mastaitis, J.W., Slieker, L. and Maratos-Flier, E. Melanin-concentrating hormone receptor is a target of leptin action in the mouse brain. Endocrinology 2001, 142: 680-6.
93. Stricker-Krongrad, A., Dimitrov, T. and Beck, B. Central and peripheral dysregulation of melanin-concentrating hormone in obese Zucker rats. Brain Res Mol Brain Res 2001, 92: 43-8.
94. Monzon, M.E. and De Barioglio, S.R. Response to novelty after i.c.v. injection of melanin-concentrating hormone (MCH) in rats. Physiol Behav 1999, 67: 813-7.
95. Monzon, M.E., Varas, M.M. and De Barioglio, S.R. Anxiogenesis induced by nitric oxide synthase inhibition and anxiolytic effect of melanin-concentrating hormone (MCH) in rat brain. Peptides 2001, 22: 1043-7.
96. Saito, Y., Cheng, M., Leslie, F.M. and Civelli, O. Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J Comp Neurol 2001, 435: 26-40.
97. Roy, M., David, N.K., Danao, J.V., Baribault, H., Tian, H. and Giorgetti, M. Genetic inactivation of melanin-concentrating hormone receptor subtype 1 (MCHR1) in mice exerts anxiolytic-like behavioral effects. Neuropsychopharmacology 2006, 31: 112-20.
98. Musselman, D.L. and Nemeroff, C.B. Depression and endocrine disorders: focus on the thyroid and adrenal system. Br J Psychiatry Suppl 1996: 123-8.
99. Drazen, D.L., Coolen, L.M., Strader, A.D., Wortman, M.D., Woods, S.C. and Seeley, R.J. Differential effects of adrenalectomy on melanin-concentrating hormone and orexin A. Endocrinology 2004, 145: 3404-12.
100. McBriar, M.D., Guzik, H., Shapiro, S. et al. Discovery of orally efficacious melanin-concentrating hormone receptor-1 antagonists as antiobesity agents. Synthesis, SAR, and biological evaluation of bicyclo[3.1.0]hexyl ureas. J Med Chem 2006, 49: 2294-310.
101. Kowalski, T.J., Farley, C., Cohen-Williams, M.E., Varty, G. and Spar, B.D. Melanin-concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size. Eur J Pharmacol 2004, 497: 41-7.
102. Haverkamp, W., Breithardt, G., Camm, A.J. et al. The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J 2000, 21: 1216-31.
103. Stenkamp, D., Mueller, S.G., Roth, G.J. et al. Preparation of arylamides as melanin concentrating hormone (MCH) receptor antagonists. 2003-EP11933 2004039764, 20031028, 2004.
104. Frimurer, T.M., Ulven, T., Hoegberg, T., Norregaard, P.K., Little, P.B. and Receveur, J.-M. Preparation of quinoline compounds for use in MCH receptor related disorders. 2003-DK857 2004052370, 20031211, 2004.
105. Frimurer, T.M., Ulven, T., Hoegberg, T., Norregaard, P.K., Little, P.B. and Receveur, J.-M. Preparation of (piperazinyl)quinoline derivatives for treatment of MCH receptor related disorders. 2003-DK858 2004052371, 20031211, 2004.
106. Ammenn, J., Gillig, J.R., Heinz, L.J. et al. Preparation of 1,3,4-oxadiazoles and related compounds for use as melanin concentrating hormone antagonists in the treatment of obesity and diabetes. 2003-US12123 2003097047, 20030506, 2003.
107. Hulme, C., Tempest, P., Ma, V., Nixey, T. and Balow, G. Preparation of tetrazolylmethylpiperazines as melanin concentrating hormone receptor antagonists. 2004-US26021 2005019167, 20040811, 2005.
108. Comuzzie, A.G., Cole, S.A., Martin, L. et al. The baboon as a nonhuman primate model for the study of the genetics of obesity. Obes Res 2003, 11: 75-80.