Therapeutic potential of melanin-concentrating hormone-1 receptor antagonists for the treatment of obesity

Expert Opinion on Investigational Drugs

Volumn 13, Issue 9, 2004, Pages 1113-1122

  Kowalski, Timothy J ^a   McBriar, Mark D ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Metabolic syndrome; Obesity; Pharmacotherapy

Indexed keywords

AMINOQUINOLINE DERIVATIVE; ANOREXIGENIC AGENT; ANTIOBESITY AGENT; AROMATIC AMINE; CYCLOHEXANE DERIVATIVE; FENFLURAMINE; HORMONE RECEPTOR; HORMONE RECEPTOR BLOCKING AGENT; IMIDAZOLE DERIVATIVE; MELANIN CONCENTRATING HORMONE; MELANIN CONCENTRATING HORMONE 1 RECEPTOR; MELANIN CONCENTRATING HORMONE 1 RECEPTOR ANTAGONIST; N (6 DIMETHYLAMINOMETHYL 5,6,7,8 TETRAHYDRO 2 NAPHTHYL) 4' FLUORO 1,1' BIPHENYL 4 CARBOXAMIDE; OXADIAZOLE DERIVATIVE; QUINOLINE DERIVATIVE; SIBUTRAMINE; SNAP 7941; TETRAHYDROLIPSTATIN; TETRALIN DERIVATIVE; TETRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

DRUG EFFICACY; DRUG INDUSTRY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENERGY BALANCE; ENERGY EXPENDITURE; EVIDENCE BASED MEDICINE; FOOD INTAKE; HUMAN; HYPOPHAGIA; IN VIVO STUDY; MEDICAL GENETICS; METABOLIC SYNDROME X; MOLECULAR WEIGHT; NONHUMAN; OBESITY; PATENT; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; WEIGHT REDUCTION;

ANIMALS; HETEROCYCLIC COMPOUNDS; HUMANS; MOLECULAR STRUCTURE; OBESITY; RECEPTORS, SOMATOSTATIN;

EID: 4544374046     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.13.9.1113     Document Type: Review

References (75)

1. FLEGAL KM, CARROLL MD, OGDEN CL, JOHNSON CL: Prevalence and trends in obesity among US adults, 1999-2000. JAMA (2002) 288(14):1723-1727.
2. MOKDAD AH, FORD ES, BOWMAN BA et al.: Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA (2003) 289(1):76-79.
3. US DEPARTMENT OF HEALTH AND HUMAN SERVICES: The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity 2001, Public Health Service. Office of the Surgeon General, Rockville, MD, USA (2001).
4. KOPELMAN, PG: Obesity as a medical problem. Nature (2000) 404(6778):635-643.
5. MUST A, SPADANO J, COAKLEY EH, FIELD AE, COLDITZ G, DIETZ WH: The disease burden associated with overweight and obesity. JAMA (1999) 282(16):1523-1529.
6. FORD ES, GILES WH, DIETZ WH: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA (2002) 287(3):356-359.
7. HAFFNER SM, VALDEZ RA, HAZUDA HP, MITCHELL BD, MORALES PA, STERN MP: Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes (1992) 41(6):715-722.
8. ISOMAA B, ALMGREN P, TUOMI T et al.: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care (2001) 24(4):683-689.
9. EXPERT PANEL ON DETECTION, EVALUATION, AND TREATMENT OF HIGH BLOOD CHOLESTEROL IN ADULTS: Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA (2001) 285(19):2486-2497.
10. WILSON PW, KANNEL WB, SILBERSHATZ H, D'AGOSTINO RB: Clustering of metabolic factors and coronary heart disease. Arch. Intern. Med. (1999) 159(10):1104-1109.
11. TUOMILEHTO J, LINDSTROM J, ERIKSSON JG et al.: Prevention of Type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. (2001) 344(18):1343-1350.
12. BAKER BI: Melanin-concentrating hormone: a general vertebrate neuropeptide. Int. Rev. Cytol. (1991) 126:1-47.
13. KAWAUCHI H, KAWAZOE I, TSUBOKAWA M, KISHIDA M, BAKER BI: Characterization of melanin-concentrating hormone in chum salmon pituitaries. Nature (1983) 305(5932):321-323.
14. PRESSE F, NAHON JL, FISCHER WH, VALE W: Structure of the human melanin concentrating hormone mRNA. Mol. Endocrinol. (1990) 4(4):632-637.
15. VAUGHAN JM, FISCHER WH, HOEGER C, RIVIER J, VALE W: Characterization of melanin-concentrating hormone from rat hypothalamus. Endocrinology (1989) 125(3):1660-1665.
16. NAHON JL, PRESSE F, BITTENCOURT JC, SAWCHENKO PE, VALE W: The rat melanin-concentrating hormone messenger ribonucleic acid encodes multiple putative neuropeptides coexpressed in the dorsolateral hypothalamus. Endocrinology (1989) 125(4):2056-2065.
17. 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(1-2):243-255.
18. BITTENCOURT JC, 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(2):218-245.
19. ELIAS CF, LEE CE, KELLY JF et al.: Characterization of CART neurons in the rat and human hypothalamus. J. Comp. Neurol. (2001) 432(1):1-19.
20. VRANG N, LARSEN PJ, CLAUSEN JT, KRISTENSEN P: Neurochemical characterization of hypothalamic cocaine-amphetamine-regulated transcript neurons. J. Neurosci. (Online) (1999) 19(10):RC5.
21. BROBERGER C: Hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons: histochemical relationship to thyrotropin-releasing hormone, melanin-concentrating hormone, orexin/hypocretin and neuropeptide Y. Brain Res. (1999) 848(1-2):101-113.
22. CHAMBERS J, AMES RS, BERGSMA D et al.: Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature (1999) 400(6741):261-265.
23. LEMBO PM, 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(5):267-271.
24. SAITO Y, NOTHACKER HP, WANG Z, LIN SH, LESLIE F, CIVELLI O: Molecular characterization of the melanin-concentrating-hormone receptor. Nature (1999) 400(6741):265-269.
25. BACHNER D, KREIENKAMP H, WEISE C, BUCK F, 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(3):522-524.
26. SHIMOMURA Y, MORI M, SUGO T et al.: Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor. Biochem. Biophys. Res. Commun. (1999) 261(3):622-626.
27. HAWES BE, KIL E, GREEN B, O'NEILL K, FRIED S, GRAZIANO MP: The melanin-concentrating hormone receptor couples to multiple G proteins to activate diverse intracellular signaling pathways. Endocrinology (2000) 141(12):4524-4532.
28. TAN CP, SANO H, IWAASA H et al.: Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression. Genomics (2002) 79(6):785-792.
29. SAITO Y, CHENG M, LESLIE FM, CIVELLI O: Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J. Comp. Neurol. (2001) 435(1):26-40.
30. 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(37):34664-34670.
31. AN S, CUTLER G, ZHAO JJ et al.: Identification and characterization of a melanin-concentrating hormone receptor. Proc. Natl. Acad. Sci. USA (2001) 98(13):7576-7581.
32. SAILER AW, SANO H, ZENG Z et al.: Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc. Natl. Acad. Sci. USA (2001) 98(13):7564-7569.
33. RODRIGUEZ M, BEAUVERGER P, NAIME I et al.: Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2. Mol. Pharmacol. (2001) 60(4):632-639.
34. 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(5):1013-1018.
35. 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(23):20125-20129.
36. FRIED S, O'NEILL K, HAWES BE: Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2. Peptides (2002) 23(8):1401-1408.
37. CHIOCCHIO SR, GALLARDO MG, LOUZAN P, GUTNISKY V, TRAMEZZANI JH: Melanin-concentrating hormone stimulates the release of luteinizing hormone-releasing hormone and gonadotropins in the female rat acting at both median eminence and pituitary levels. Biol. Reprod. (2001) 64(5):1466-1472.
38. TSUKAMURA H, THOMPSON RC, TSUKAHARA S et al.: Intracerebroventricular administration of melanin-concentrating hormone suppresses pulsatile luteinizing hormone release in the female rat. J. Neuroendocrinol. (2000) 12(6):529-534.
39. MURRAY JF, ADAN RA, WALKER R et al.: Melanin-concentrating hormone, melanocortin receptors and regulation of luteinizing hormone release. J. Neuroendocrinol. (2000) 12(3):217-223.
40. GONZALEZ MI, BAKER BI, WILSON CA: Stimulatory effect of melanin-concentrating hormone on luteinising hormone release. Neuroendocrinology (1997) 66(4):254-262.
41. KENNEDY AR, TODD JF, DHILLO WS 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(3):268-272.
42. BLUET-PAJOT MT, 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(4):297-303.
43. JEZOVA D, BARTANUSZ V, WESTERGREN I et al.: Rat melanin-concentrating hormone stimulates adrenocorticotropin secretion: evidence for a site of action in brain regions protected by the blood-brain barrier. Endocrinology (1992) 130(2):1024-1029.
44. KELA J, SALMI P, RIMONDINI-GIORGINI R, HEILIG M, WAHLESTEDT C: Behavioural analysis of melanin-concentrating hormone in rats: evidence for orexigenic and anxiolytic properties. Regul. Pept. (2003) 114(2-3):109-114.
45. MONZON ME, DE BARIOGLIO SR: Response to novelty after i.c.v. injection of melanin-concentrating hormone (MCH) in rats. Physiol. Behav. (1999) 67(5):813-817.
46. ELIAS CF, SAPER CB, MARATOS-FLIER E et al.: Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J. Comp. Neurol. (1998) 402(4):442-459.
47. HANADA R, NAKAZATO M, MATSUKURA S, MURAKAMI N, YOSHIMATSU H, SAKATA T: Differential regulation of melanin-concentrating hormone and orexin genes in the agouti-related protein/melanocortin-4 receptor system. Biochem. Biophys. Res. Commun. (2000) 268(1):88-91.
48. QU D, LUDWIG DS, GAMMELTOFT S et al.: A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature (1996) 380(6571):243-247.
49. DELLA-ZUANA O, PRESSE F, ORTOLA C, DUHAULT J, NAHON JL, 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. Relat. Metab. Disord. (2002) 26(10):1289-1295.
50. ROSSI M, CHOI SJ, O'SHEA D, MIYOSHI T, GHATEI MA, BLOOM SR: Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight. Endocrinology (1997) 138(1):351-355.
51. LUDWIG DS, MOUNTJOY KG, TATRO JB et al.: Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus. Am. J. Physiol. (1998) 274(4 Pt 1):E627-633.
52. TRITOS NA, VICENT D, GILLETTE J, LUDWIG DS, FLIER ES, MARATOS-FLIER E: Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. Diabetes (1998) 47(11):1687-1692.
53. STRICKER-KRONGRAD A, DIMITROV T, BECK B: Central and peripheral dysregulation of melanin-concentrating hormone in obese Zucker rats. Brain Res. Mol. Brain Res. (2001) 92(1-2):43-48.
54. SERGEYEV V, BROBERGER C, GORBATYUK O, 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(1):117-121.
55. ITO M, GOMORI A, ISHIHARA A et al.: Characterization of MCH-mediated obesity in mice. Am. J. Physiol. Endocrinol. Metab. (2003) 284(5):E940-945.
56. GOMORI A, ISHIHARA A, ITO M et al.: Chronic intracerebroventricular infusion of MCH causes obesity in mice. Am. J. Physiol. Endocrinol. Metab. (2003) 284(3):E583-E588.
57. SHEARMAN LP, CAMACHO RE, STRIBLING DS et al.: Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. Eur. J. Pharmacol. (2003) 475(1-3):37-47.
58. LUDWIG DS, TRITOS NA, MASTAITIS JW et al.: Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J. Clin. Invest. (2001) 107(3):379-386.
59. SHIMADA M, TRITOS NA, LOWELL BB, FLIER JS, MARATOS-FLIER E: Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature (1998) 396(6712):670-674.
60. SEGAL-LIEBERMAN G, BRADLEY RL, KOKKOTOU E et al.: Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc. Natl. Acad. Sci. USA (2003) 100(17):10085-10090.
61. CHEN Y, HU C, HSU CK et al.: Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology (2002) 143(7):2469-2477.
62. MARSH DJ, WEINGARTH DT, NOVI DE et al.: Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc. Natl. Acad. Sci. USA (2002) 99(5):3240-3245.
63. ASTRAND A, BOHLOOLY-Y M, LARSDOTTER S et al.: Mice lacking the melanin concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity. Am. J. Physiol. (2004) (In press).
64. CARTPENTER AJ, HERTZOG DL: Melanin-concentrating hormone receptor antagonists as potential anti-obesity agents. Expert Opin. Ther. Patents (2002) 12:1639-1646.
65. BROWNING A: Recent developments in the discovery of melanin-concentrating hormone antagonists: novel antiobesity agnets. Expert Opin. Ther. Patents (2004) 14:313-325.
66. COLLINS CA, KYM PR: Prospects for obesity treatment: MCH receptor antagonists. Curr. Opin. Investig. Drugs (2003) 4(4):386-394.
67. HUNT H: 12th RSC-SCI Symposium. Cambridge, UK (2003) IDDB reference 506101.
68. ADESSI C, SOTO C: Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr. Med. Chem. (2002) 9(9):963-978.
69. CHEN X, WANG W: The use of bioisosteric groups in lead optimization. In: Annual Reports in Medicinal Chemistry (Volume 38). DOHERTY AM (Ed.), Elsevier Academic Press, San Diego, CA, USA (2003):333-346.
70. TEMPEST PA, NIXEY T, MA V et al.: Novel potent tetrazole containing melanin concentrating hormone (MCH) receptor antagonists - multi-component reactions lead the way. 227th American Chemical Society Annual Meeting, Anaheim, CA, USA (2004) MEDI298.
71. 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(3):129-135.
72. BOROWSKY B, DURKIN MM, OGOZALEK K et al.: Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat. Med. (2002) 8(8):825-830.
73. BEDNAREK MA, HRENIUK DL, 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(20):6383-6390.
74. +)SNAP-7941, in models of potential antidepressant and anxiolytic activity in rodents. Eur. J. Neuropsychopharmacol. (2003) 13(Suppl. 4):S268.
75. BOHLOOLY-Y M, MAHLAPUU M, ANDERSEN H et al.: Osteoporosis in MCHR1-deficient mice. Biochem. Biophys. Res. Commun. (2004) 318:964-969.