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Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options

DOI: 10.3390/ph3010125

Keywords: obesity, drug treatment, orlistat, sibutramine, rimonabant, leptin, ghrelin

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Abstract:

Available anti-obesity pharmacotherapy options remain very limited and development of more effective drugs has become a priority. The potential strategies to achieve weight loss are to reduce energy intake by stimulating anorexigenic signals or by blocking orexigenic signals, and to increase energy expenditure. This review will focus on approved obesity medications, as well as potential new pharmacologic treatment options.

References

[1]  En?, F.Y.; Ones, T.; Akin, H.L.; Dede, F.; Turo?lu, H.T.; Ulfer, G.; Bekiro?lu, N.; Haklar, G.; Rehfeld, J.F.; Holst, J.J.; Ulusoy, N.; Imeryüz, N. Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects. Am. J. Physiol. Gastrointest. Liver Physiol.?2009, 296, 482–489, doi:10.1152/ajpgi.90209.2008.
[2]  Li, Z.; Maglione, M.; Tu, W.; Mojica, W.; Arterburn, D.; Shugarman, L.R.; Hilton, L.; Suttorp, M.; Solomon, V.; Shekelle, P.G.; Morton, S.C. Meta-analysis: pharmacologic treatment of obesity. Ann. Intern. Med.?2005, 142, 532–546. 15809465
[3]  Rucker, D.; Padwal, R; Li, S.K.; Curioni, C.; Lau, D.C. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ?2007, 335, 1194–1199, doi:10.1136/bmj.39385.413113.25. 18006966
[4]  Christensen, R.; Kristensen, P.K.; Bartels, E.M.; Bliddal, H.; Astrup, A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet?2007, 370, 1706–1713, doi:10.1016/S0140-6736(07)61721-8. 18022033
[5]  Torgerson, J.S.; Hauptman, J.; Boldrin, M.N.; Sj?str?m, L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diab. Care?2004, 27, 155–161, doi:10.2337/diacare.27.1.155.
[6]  Bérubé-Parent, S.; Prud′homme, D.; St-Pierre, S.; Doucet, E; Tremblay, A. Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet--exercise intervention. Int. J. Obes,?2001, 25, 1144–1153, doi:10.1038/sj.ijo.0801677.
[7]  Bellocchio, L.; Cervino, C.; Pasquali, R.; Pagotto, R. The endocannabinoid system and energy metabolism. J. Neuroendocrinol.?2008, 20, 850–857, doi:10.1111/j.1365-2826.2008.01728.x. 18601709
[8]  Akbas, F.; Gasteyger, C.; Sj?din, A.; Astrup, A.; Larsen, T.M. A critical review of the cannabinoid receptor as a drug target for obesity management. Obes. Rev.?2008, 10, 58–67, doi:10.1111/j.1467-789X.2008.00520.x. 18721231
[9]  Addy, C.; Li, S.; Agrawal, N.; Stone, J.; Majumdar, A.; Zhong, L.; Li, H.; Yuan, J.; Maes, A.; Rothenberg, P.; Cote, J.; Rosko, K.; Cummings, C.; Warrington, S.; Boyce, M.; Gottesdiener, K.; Stoch, A.; Wagner, J. Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, for the treatment of obesity: results from a double-blind, placebo-controlled, single oral dose study in healthy volunteers. J. Clin. Pharmacol.?2008, 48, 418–427, doi:10.1177/0091270008314467. 18258750
[10]  Addy, C.; Wright, H.; Van Laere, K.; Gantz, I.; Erondu, N.; Musser, B.J.; Lu, K.; Yuan, J.; Sanabria-Bohórquez, S.M.; Stoch, A.; Stevens, C.; Fong, T.M.; De Lepeleire, I.; Cilissen, C.; Cote, J.; Rosko, K.; Gendrano 3rd, I.N.; Nguyen, A.M.; Gumbiner, B.; Rothenberg, P.; de Hoon, J.; Bormans, G.; Depré, M.; Eng, W.S.; Ravussin, E.; Klein, S.; Blundell, J.; Herman, G.A.; Burns, H.D.; Hargreaves, R.J.; Wagner, J.; Gottesdiener, K.; Amatruda, J.M.; Heymsfield, S.B. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab.?2008, 7, 68–78, doi:10.1016/j.cmet.2007.11.012. 18177726
[11]  Lamota, L.; Bermudez-Silva, F.J.; Marco, E.M.; Llorente, R.; Gallego, A.; Rodríguez de Fonseca, F.; Viveros, M.P. Effects of adolescent nicotine and SR 147778 (Surinabant) administration on food intake, somatic growth and metabolic parameters in rats. Neuropharmacology?2008, 54, 194–205, doi:10.1016/j.neuropharm.2007.07.004. 17720206
[12]  Song, K.S.; Kim, M.J.; Seo, H.J.; Lee, S.H.; Jung, M.E.; Kim, S.U.; Kim, J.; Lee, J. Synthesis and structure-activity relationship of novel diarylpyrazole imide analogues as CB1 cannabinoid receptor ligands. Bioorg. Med. Chem.?2009, 17, 3080–3092, doi:10.1016/j.bmc.2009.03.006. 19328001
[13]  Foster-Schubert, K.E.; Cummings, D.E. Emerging therapeutic strategies for obesity. Endocr. Rev.?2006, 27, 779–793. 17122357
[14]  Cawthorne, M.A. Opportunities and challenges for the development of pharmacological therapies for obesity treatment. Obes. Rev.?2007, 8 (Suppl. 1), 131–136, doi:10.1111/j.1467-789X.2007.00332.x. 17316316
[15]  Oh, S.; Kim, K.S.; Chung, Y.S.; Shong, M.; Park, S.B. Anti-obesity agents: a focused review on the structural classification of therapeutic entities. Curr. Top. Med. Chem.?2009, 9, 466–481, doi:10.2174/156802609788897862.
[16]  Klok, M.D.; Jakobsdottir, S.; Drent, M.L. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: A review. Obes. Rev.?2007, 8, 21–34, doi:10.1111/j.1467-789X.2006.00270.x.
[17]  Considine, R.V.; Sinha, M.K.; Heiman, M.L.; Kriauciunas, A.; Stephens, T.W.; Nyce, M.R.; Ohannesian, J.P.; Marco, C.C.; McKee, L.J.; Bauer, T.L.; Caro, J.F. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med.?1996, 334, 292–295, doi:10.1056/NEJM199602013340503. 8532024
[18]  Schwartz, M.W.; Seeley, R.J.; Campfield, L.A.; Burn, P.; Baskin, D.G. Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest.?1996, 98, 1101–1106, doi:10.1172/JCI118891. 8787671
[19]  Otvos Jr., L.; Terrasi, M.; Cascio, S.; Cassone, M.; Abbadessa, G.; De Pascali, F.; Scolaro, L.; Knappe, D.; Stawikowski, M.; Cudic, P.; Wade, J.D.; Hoffmann, R.; Surmacz, E. Development of a pharmacologically improved peptide agonist of the leptin receptor. Biochim. Biophys. Acta?2008, 1783, 1745–1754, doi:10.1016/j.bbamcr.2008.05.007. 18555805
[20]  Banks, W.A. Leptin transport across the blood-brain barrier: implications for the cause and treatment of obesity. Curr. Pharm. Des.?2001, 7, 125–133, doi:10.2174/1381612013398310. 11172704
[21]  El-Haschimi, K.; Pierroz, D.D.; Hileman, S.M.; Bjorbaek, C.; Flier, J.S. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J. Clin. Invest.?2000, 105, 1827–1832, doi:10.1172/JCI9842. 10862798
[22]  Huszar, D.; Lynch, C.A.; Fairchild-Huntress, V.; Dunmore, J.H.; Fang, Q.; Berkemeier, L.R.; Gu, W.; Kesterson, R.A.; Boston, B.A.; Cone, R.D.; Smith, F.J.; Campfield, L.A.; Burn, P.; Lee, F. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell?1997, 88, 131–141, doi:10.1016/S0092-8674(00)81865-6. 9019399
[23]  Chen, A.S.; Marsh, D.J.; Trumbauer, M.E.; Frazier, E.G.; Guan, X.M.; Yu, H.; Rosenblum, C.I.; Vongs, A.; Feng, Y.; Cao, L.; Metzger, J.M.; Strack, A.M.; Camacho, R.E.; Mellin, T.N.; Nunes, C.N.; Min, W.; Fisher, J.; Gopal-Truter, S.; MacIntyre, D.E.; Chen, H.Y.; Van der Ploeg, L.H. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet.?2000, 26, 97–102, doi:10.1038/79254. 10973258
[24]  Benoit, S.C.; Schwartz, M.W.; Lachey, J.L.; Hagan, M.M.; Rushing, P.A.; Blake, K.A.; Yagaloff, K.A.; Kurylko, G.; Franco, L.; Danhoo, W.; Seeley, R.J. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci.?2000, 20, 3442–3448. 10777807
[25]  Mancini, M.C.; Halpern, A. Investigational therapies in the treatment of obesity. Expert Opin. Investig. Drugs?2006, 15, 897–915, doi:10.1517/13543784.15.8.897. 16859393
[26]  Coll, A.P. Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential? Clin. Sci.?2007, 113, 171–182, doi:10.1042/CS20070105. 17623013
[27]  ALS CNTF Treatment Study Group. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology?1996, 46, 1244–1249. 8628460
[28]  Ettinger, M.P.; Littlejohn, T.W.; Schwartz, S.L.; Weiss, S.R.; McIlwain, H.H.; Heymsfield, S.B.; Bray, G.A.; Roberts, W.G.; Heyman, E.R.; Stambler, N.; Heshka, S.; Vicary, C.; Guler, H.P. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: A randomized, dose-ranging study. JAMA?2003, 289, 1826–1832, doi:10.1001/jama.289.14.1826. 12684362
[29]  Febbraio, M.A. gp130 receptor ligands as potential therapeutic targets for obesity. J. Clin. Invest.?2007, 117, 841–849, doi:10.1172/JCI30453. 17404609
[30]  Matthews, V.B.; Febbraio, M.A. CNTF: A target therapeutic for obesity-related metabolic disease? J. Mol. Med.?2008, 86, 353–361, doi:10.1007/s00109-007-0286-y. 18210031
[31]  Tecott, L.H.; Sun, L.M.; Akana, S.F.; Strack, A.M.; Lowenstein, D.H.; Dallman, M.F.; Julius, D. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature?1995, 374, 542–546, doi:10.1038/374542a0. 7700379
[32]  Nonogaki, K.; Strack, A.M.; Dallman, M.F.; Tecott, L.H. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med.?1998, 4, 1152–1156, doi:10.1038/2647.
[33]  Heisler, L.K.; Jobst, E.E.; Sutton, G.M.; Zhou, L.; Borok, E.; Thornton-Jones, Z.; Liu, H.Y.; Zigman, J.M.; Balthasar, N.; Kishi, T.; Lee, C.E.; Aschkenasi, C.J.; Zhang, C.Y.; Yu, J.; Boss, O.; Mountjoy, K.G.; Clifton, P.G.; Lowell, B.B.; Friedman, J.M.; Horvath, T.; Butler, A.A.; Elmquist, J.K.; Cowley, M.A. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron?2006, 51, 239–249, doi:10.1016/j.neuron.2006.06.004. 16846858
[34]  Halford, J.C.; Harrold, J.A.; Boyland, E.J.; Lawton, C.L.; Blundell, J.E. Serotonergic drugs : effects on appetite expression and use for the treatment of obesity. Drugs?2007, 67, 27–55, doi:10.2165/00003495-200767010-00004. 17209663
[35]  Wacker, D.A.; Miller, K.J. Agonists of the serotonin 5-HT2C receptor: preclinical and clinical progression in multiple diseases. Curr. Opin. Drug Discov. Devel.?2008, 11, 438–435. 18600561
[36]  Holenz, J.; Mercè, R.; Díaz, J.L.; Guitart, X.; Codony, X.; Dordal, A.; Romero, G.; Torrens, A.; Mas, J.; Andaluz, B.; Hernández, S.; Monroy, X.; Sánchez, E.; Hernández, E.; Pérez, R.; Cubí, R.; Sanfeliu, O.; Buschmann, H. Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands. J. Med. Chem.?2005, 48, 1781–1795, doi:10.1021/jm049615n. 15771424
[37]  Holenz, J.; Pauwels, P.J.; Díaz, J.L.; Mercè, R.; Codony, X.; Buschmann, H. Medicinal chemistry strategies to 5-HT(6) receptor ligands as potential cognitive enhancers and anti-obesity agents. Drug Discov. Today?2006, 11, 283–299, doi:10.1016/j.drudis.2006.02.004. 16580970
[38]  Heal, D.J.; Smith, S.L.; Fisas, A.; Codony, X.; Buschmann, H. Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol. Ther.?2008, 117, 207–231, doi:10.1016/j.pharmthera.2007.08.006. 18068807
[39]  Kamiji, M.M.; Inui, A. Neuropeptide y receptor selective ligands in the treatment of obesity. Endocr. Rev.?2007, 28, 664–684, doi:10.1210/er.2007-0003. 17785427
[40]  Luthin, D.R. Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life Sci.?2007, 81, 423–440, doi:10.1016/j.lfs.2007.05.029. 17655875
[41]  Kym, P.R. Lead optimization strategies and tactics applied to the discovery of melanin concentrating hormone receptor 1 antagonists. Curr. Top. Med. Chem.?2007, 7, 1471–1488, doi:10.2174/156802607782194699. 17897033
[42]  Rivera, G.; Bocanegra-García, V.; Galiano, S.; Cirauqui, N.; Ceras, J.; Pérez, S.; Aldana, I.; Monge, A. Melanin-concentrating hormone receptor 1 antagonists: A new perspective for the pharmacologic treatment of obesity. Curr. Med. Chem.?2008, 15, 1025–1043, doi:10.2174/092986708784049621. 18393860
[43]  Lustig, R.H.; Greenway, F.; Velasquez-Mieyer, P.; Heimburger, D.; Schumacher, D.; Smith, D.; Smith, W.; Soler, N.; Warsi, G.; Berg, W.; Maloney, J.; Benedetto, J.; Zhu, W.; Hohneker, J. A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion. Int. J. Obes. (Lond.)?2006, 30, 331–341, doi:10.1038/sj.ijo.0803074. 16158082
[44]  Velasquez-Mieyer, P.A.; Cowan, P.A.; Arheart, K.L.; Buffington, C.K.; Spencer, K.A.; Connelly, B.E.; Cowan, G.W.; Lustig, R.H. Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults. Int. J. Obes. Relat. Metab. Disord.?2003, 27, 219–226, doi:10.1038/sj.ijo.802227. 12587002
[45]  Huda, M.S.; Wilding, J.P.; Pinkney, J.H. Gut peptides and the regulation of appetite. Obes. Rev.?2006, 7, 163–182, doi:10.1111/j.1467-789X.2006.00245.x. 16629873
[46]  Murphy, K.G.; Dhillo, W.S.; Bloom, S.R. Gut peptides in the regulation of food intake and energy homeostasis. Endocr. Rev.?2006, 27, 719–727, doi:10.1210/er.2005-0011. 17077190
[47]  Cummings, D.E.; Overduin, J. Gastrointestinal regulation of food intake. J. Clin. Invest.?2007, 117, 13–23, doi:10.1172/JCI30227. 17200702
[48]  Field, B.C.; Wren, A.M.; Cooke, D.; Bloom, S.R. Gut hormones as potential new targets for appetite regulation and the treatment of obesity. Drugs?2008, 68, 147–163, doi:10.2165/00003495-200868020-00002. 18197723
[49]  Meier, J.J.; Nauck, M.A. Glucagon-like peptide 1(GLP-1) in biology and pathology. Diabetes Metab. Res. Rev.?2005, 21, 91–117, doi:10.1002/dmrr.538. 15759282
[50]  Rodríguez de Fonseca, F.; Navarro, M.; álvarez, E.; Roncero, I.; Chowen, J.A.; Maestre, O.; Gómez, R.; Mu?oz, R.M.; Eng, J.; Blázquez, E. Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats. Metabolism?2000, 49, 709–717, doi:10.1053/meta.2000.6251. 10877194
[51]  Flint, A.; Raben, A.; Astrup, A.; Holst, J.J. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest.?1998, 101, 515–520, doi:10.1172/JCI990. 9449682
[52]  Gutzwiller, J.P.; G?ke, B.; Drewe, J.; Hildebrand, P.; Ketterer, S.; Handschin, D.; Winterhalder, R.; Conen, D.; Beglinger, C. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut?1999, 44, 81–86. 9862830
[53]  Meier, J.J.; Gallwitz, B.; Schmidt, W.E.; Nauck, M.A. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur. J. Pharmacol.?2002, 440, 269–279, doi:10.1016/S0014-2999(02)01434-6. 12007541
[54]  Batterham, R.L.; Cowley, M.A.; Small, C.J.; Herzog, H.; Cohen, M.A.; Wren, A.M.; Brynes, A.E.; Low, M.; Ghatei, M.A.; Cone, R.D.; Bloom, S.R. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature?2002, 418, 650–654, doi:10.1038/nature00887. 12167864
[55]  Acu?a-Goycolea, C.; van den Pol, A.N. Peptide YY(3-36) inhibits both anorexigenic proopiomelanocortin and orexigenic neuropeptide Y neurons: implications for hypothalamic regulation of energy homeostasis. J. Neurosci.?2005, 25, 10510–10519, doi:10.1523/JNEUROSCI.2552-05.2005. 16280589
[56]  Wynne, K.; Bloom, S.R. The role of oxyntomodulin and peptide tyrosine-tyrosine (PYY) in appetite control. Nat. Clin. Pract. Endocrinol. Metab.?2006, 2, 612–620, doi:10.1038/ncpendmet0318. 17082808
[57]  Vincent, R.P.; le Roux, C.W. The satiety hormone peptide YY as a regulator of appetite. J. Clin. Pathol.?2008, 61, 548–552, doi:10.1136/jcp.2007.048488. 18441153
[58]  Pérez-Fontán, M.; Cordido, F.; Rodríguez-Carmona, A.; Penín, M.; Díaz-Cambre, H.; López-Mu?iz, A.; Sangiao-Alvarellos, S.; García-Buela, J. Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure. Nephrol. Dial. Transplant.?2008, 23, 3696–3703, doi:10.1093/ndt/gfn297. 18503008
[59]  Pérez-Fontán, M.; Cordido, F.; Rodríguez-Carmona, A.; Peteiro, J.; García-Naveiro, R.; García-Buela, J. Plasma ghrelin levels in patients undergoing haemodialysis and peritoneal dialysis. Nephrol. Dail. Transplant.?2004, 19, 2095–2100, doi:10.1093/ndt/gfh313.
[60]  Pérez-Fontán, M.; Cordido, F.; Rodríguez-Carmona, A.; García-Naveiro, R.; Isidro, M.L.; Villaverde, P.; García-Buela, J. Acute plasma ghrelin and leptin responses to oral feeding or intraperitoneal hypertonic glucose-based dialysate in patients with chronic renal failure. Kidney Int.?2005, 68, 2877–2885, doi:10.1111/j.1523-1755.2005.00761.x. 16316365
[61]  Druce, M.R.; Wren, A.M.; Park, A.J.; Milton, J.E.; Patterson, M.; Frost, G.; Ghatei, M.A.; Small, C.; Bloom, S.R. Ghrelin increases food intake in obese as well as lean subjects. Int. J. Obes. (Lond.)?2005, 29, 1130–1136, doi:10.1038/sj.ijo.0803001. 15917842
[62]  English, P.J.; Ghatei, M.A.; Malik, I.A.; Bloom, S.R.; Wilding, J.P. Food fails to suppress ghrelin levels in obese humans. J. Clin. Endocrinol. Metab.?2002, 87, 2984–2987, doi:10.1210/jc.87.6.2984. 12050284
[63]  Zhao, H.; Xin, Z.; Liu, G.; Schaefer, V.G.; Falls, H.D.; Kaszubska, W.; Collins, C.A.; Sham, H.L. Discovery of tetralin carboxamide growth hormone secretagogue receptor antagonists via scaffold manipulation. J. Med. Chem.?2004, 47, 6655–6657, doi:10.1021/jm0491750. 15615511
[64]  Rudolph, J.; Esler, W.P.; O'connor, S.; Coish, P.D.; Wickens, P.L.; Brands, M.; Bierer, D.E.; Bloomquist, B.T.; Bondar, G.; Chen, L.; Chuang, C.Y.; Claus, T.H.; Fathi, Z.; Fu, W.; Khire, U.R.; Kristie, J.A.; Liu, X.G.; Lowe, D.B.; McClure, A.C.; Michels, M.; Ortiz, A.A.; Ramsden, P.D.; Schoenleber, R.W.; Shelekhin, T.E.; Vakalopoulos, A.; Tang, W.; Wang, L.; Yi, L.; Gardell, S.J.; Livingston, J.N.; Sweet, L.J.; Bullock, W.H. Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity. J. Med. Chem.?2007, 50, 5202–5216, doi:10.1021/jm070071+. 17887659
[65]  Esler, W.P.; Rudolph, J.; Claus, T.H.; Tang, W.; Barucci, N.; Brown, S.E.; Bullock, W.; Daly, M.; Decarr, L.; Li, Y.; Milardo, L.; Molstad, D.; Zhu, J.; Gardell, S.J.; Livingston, J.N.; Sweet, L.J. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology?2007, 148, 5175–5185, doi:10.1210/en.2007-0239. 17656463
[66]  Moulin, A.; Demange, L.; Ryan, J.; Mousseaux, D.; Sanchez, P.; Bergé, G.; Gagne, D.; Perrissoud, D.; Locatelli, V.; Torsello, A.; Galleyrand, J.C.; Fehrentz, J.A.; Martinez, J. New trisubstituted 1,2,4-triazole derivatives as potent ghrelin receptor antagonists. 3. Synthesis and pharmacological in vitro and in vivo evaluations. J. Med. Chem. ?2008, 51, 689–693. 18193826
[67]  Beck, B.; Richy, S.; Stricker-Krongrad, A. Feeding response to ghrelin agonist and antagonist in lean and obese Zucker rats. Life Sci.?2004, 76, 473–478, doi:10.1016/j.lfs.2004.09.001. 15530508
[68]  Halem, H.A.; Taylor, J.E.; Dong, J.Z.; Shen, Y.; Datta, R.; Abizaid, A.; Diano, S.; Horvath, T.; Zizzari, P.; Bluet-Pajot, M.T.; Epelbaum, J.; Culler, M.D. Novel analogues of ghrelin: physiological and clinical implications. Eur. J. Endocrinol?2004, 151(Suppl.1), S71–S75, doi:10.1530/eje.0.151S071. 15339248
[69]  Holst, B.; Cygankiewicz, A.; Jensen, T.H.; Ankersen, M.; Schwartz, T.W. High constitutive signaling of the ghrelin receptor-identification of a potent inverse agonist. Mol. Endocrinol.?2003, 17, 2201–2210, doi:10.1210/me.2003-0069. 12907757
[70]  Helmling, A.; Maasch, C.; Eulberg, D.; Buchner, K.; Sch?der, W.; Lange, C.; Vonhoff, S.; Wlotzka, B.; Tsch?p, M.H.; Rosewicz, S.; Klussmann, S. Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc. Natl. Acad. Sci. USA?2004, 101, 13174–13179, doi:10.1073/pnas.0404175101.
[71]  Zorrilla, E.P.; Iwasaki, S.; Moss, J.A.; Chang, J.; Otsuji, J.; Inoue, K.; Meijler, M.M; Janda, K.D. Vaccination against weight gain. Proc. Natl. Acad. Sci. USA?2006, 103, 13226–31321, doi:10.1073/pnas.0605376103.
[72]  Kobelt, P.; Helmling, S.; Stengel, A.; Wlotzka, B.; Andresen, V.; Klapp, B.F.; Wiedenmann, B.; Klussmann, S.; M?nnikes, H. Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats. Gut?2006, 55, 788–792, doi:10.1136/gut.2004.061010. 15994217
[73]  Shearman, L.P.; Wang, S.P.; Helmling, S.; Stribling, D.S.; Mazur, P.; Ge, L.; Wang, L.; Klussmann, S.; Macintyre, D.E.; Howard, A.D.; Strack, A.M. Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice. Endocrinology?2006, 147, 1517–1526, doi:10.1210/en.2005-0993. 16339202
[74]  Bataille, D.; Gespach, C.; Tatemoto, K.; Marie, J.C.; Coudray, A.M.; Rosselin, G.; Mutt, V. Bioactive enteroglucagon (oxyntomodulin): present knowledge on its chemical structure and its biological activities. Peptides?1981, 2 (Suppl. 2), S41–S44, doi:10.1016/0196-9781(81)90008-5.
[75]  Dakin, C.L.; Gunn, I.; Small, C.J.; Edwards, C.M.; Hay, D.L.; Smith, D.M.; Ghatei, M.A.; Bloom, S.R. Oxyntomodulin inhibits food intake in the rat. Endocrinology?2001, 142, 4244–4250, doi:10.1210/en.142.10.4244. 11564680
[76]  Dakin, C.L.; Small, C.J.; Batterham, R.L.; Neary, N.M.; Cohen, M.A.; Patterson, M.; Ghatei, M.A.; Bloom, S.R. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology?2004, 145, 2687–2695, doi:10.1210/en.2003-1338. 15001546
[77]  Cohen, M.A.; Ellis, S.M.; Le Roux, C.W.; Batterham, R.L.; Park, A.; Patterson, M.; Frost, G.S.; Ghatei, M.A.; Bloom, S.R. Oxyntomodulin suppresses appetite and reduces food intake in humans. J. Clin. Endocrinol. Metab.?2003, 88, 4696–4701, doi:10.1210/jc.2003-030421. 14557443
[78]  Wynne, K.; Park, A.J.; Small, C.J.; Meeran, K.; Ghatei, M.A.; Frost, G.S.; Bloom, S.R. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: A randomised controlled trial. Int. J. Obes. (Lond.)?2006, 30, 1729–1736, doi:10.1038/sj.ijo.0803344. 16619056
[79]  Wynne, K.; Bloom, S.R. The role of oxyntomodulin and peptide tyrosine-tyrosine (PYY) in appetite control. Nat. Clin. Pract. Endocrirnol. Metab.?2006, 2, 612–620, doi:10.1038/ncpendmet0318.
[80]  Clapham, J.C.; Arch, J.R. Thermogenic and metabolic anti-obesity drugs: Rationale and opportunities. Diabetes, Obes. Metab.?2007, 9, 259–275, doi:10.1111/j.1463-1326.2006.00608.x.
[81]  Buemann, B.; Toubro, S.; Astrup, A. Effects of the two beta3-agonists, ZD7114 and ZD2079 on 24 hour energy expenditure and respiratory quotient in obese subjects. Int. J. Obes. Relat. Metab. Disord.?2000, 24, 1553–1560, doi:10.1038/sj.ijo.0801452. 11126205
[82]  Arch, J.R. beta(3)-Adrenoceptor agonists: potential, pitfalls and progress. Eur. J. Pharmacol.?2002, 440, 99–107, doi:10.1016/S0014-2999(02)01421-8. 12007528
[83]  Larsen, T.M.; Toubro, S.; van Baak, M.A.; Gottesdiener, K.M.; Larson, P.; Saris, W.H.; Astrup, A. Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am. J. Clin. Nutr.?2002, 76, 780–788, doi:10.1016/S0014-2999(02)01421-8. 12007528
[84]  Redman, L.M.; de Jonge, L.; Fang, X.; Gamlin, B.; Recker, D.; Greenway, F.L.; Smith, S.; Ravussin, E. Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study. J. Clin. Endocrinol. Metab.?2007, 92, 527–531, doi:10.1210/jc.2006-1740. 17118998
[85]  álvarez-Castro, P.; Isidro, M.L.; García-Buela, J.; Leal-Cerro, A.; Broglio, F.; Tassone, F.; Ghigo, E.; Diéguez, C.; Casanueva, F.F.; Cordido, F. Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients. Clin. Endocrinol. (Oxf.)?2004, 61, 250–255, doi:10.1111/j.1365-2265.2004.02092.x. 15272922
[86]  Cordido, F.; álvarez-Castro, P.; Isidro, M.L.; Casanueva, F.F.; Diéguez, C. Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients. Eur. J. Endocrinol.?2003, 149, 117–122, doi:10.1530/eje.0.1490117. 12887288
[87]  Mekala, K.C.; Tritos, N.A. Effects of recombinant human growth hormone therapy in obesity in adults: a meta analysis. J. Clin. Endocrinol. Metab.?2009, 1, 130–137.
[88]  Ng, F.M.; Sun, J.; Sharma, L.; Libinaka, R.; Jiang, W.J.; Gianello, R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm. Res.?2000, 53, 274–278, doi:10.1159/000053183. 11146367
[89]  Heffernan, M.; Summers, R.J.; Thorburn, A.; Ogru, E.; Gianello, R.; Jiang, W.J.; Ng, F.M. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology?2001, 142, 5182–5189, doi:10.1210/en.142.12.5182. 11713213
[90]  Costford, S.; Gowing, A.; Harper, M.E. Mitochondrial uncoupling as a target in the treatment of obesity. Curr. Opin. Clin. Nutr. Metab. Care.?2007, 10, 671–678, doi:10.1097/MCO.0b013e3282f0dbe4. 18089946
[91]  Ioannides-Demos, L.L.; Proietto, J.; Tonkin, A.M.; McNeil, J.J. Safety of drug therapies used for weight loss and treatment of obesity. Drug. Saf.?2006, 29, 277–302, doi:10.2165/00002018-200629040-00001. 16569079
[92]  Elangbam, C.S. Review paper: Current strategies in the development of anti-obesity drugs and their safety concerns. Vet. Pathol.?2009, 46, 10–24, doi:10.1354/vp.46-1-10. 19112110
[93]  Early Communication about an Ongoing Safety Review of Meridia (sibutramine hydrochloride). Available online: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm191650.htm , accessed on January 11, 2010.
[94]  Astrup, A.; Madsbad, S.; Breum, L.; Jensen, T.J.; Kroustrup, J.P.; Larsen, T.M. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet?2008, 372, 1906–1913, doi:10.1016/S0140-6736(08)61525-1. 18950853

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