Drug strategies for the treatment of obesity

IDrugs

Volumn 6, Issue 6, 2003, Pages 566-572

  Alemany, Marià ^a   Remesar, Xavier ^a   Fernández López, Jose Antonio ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Anti obesity drugs; Appetite control; Hypothalamic neuropeptides; Thermogenesis

Indexed keywords

2,3,4,5 TETRAHYDRO 7,8 DIHYDROXY 1 PHENYL 1H 3 BENZAZEPINE; 3 (3,4 DIHYDROXYPHENYL) 2 [3 (4 FLUOROPHENYL)PROPYLAMINO] 3 HYDROXYPROPIONIC ACID PYRROLIDINE AMIDE; 4 (3 TERT BUTYLAMINO 2 HYDROXYPROPOXY) 2 BENZIMIDAZOLONE; 4 [(4 BROMO 2 CYANOPHENYL)CARBAMOYL]BENZYLPHOSPHONIC ACID DIETHYL ESTER; 4 [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]ETHOXY]PHENYLACETIC ACID; 4 [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]PROPYL]BENZOIC ACID; 4 [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]PROPYL]BENZOIC ACID METHYL ESTER HYDROGEN MALEATE; 4 [2 [(2 HYDROXY 3 PHENOXYPROPYL)AMINO]ETHOXY] N (2 METHOXYETHYL)PHENOXYACETAMIDE; 4 [2 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]PROPYL]PHENOXYACETIC ACID; 4 [2 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]PROPYL]PHENOXYACETIC ACID METHYL ESTER; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; 5 [2 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]PROPYL] 1,3 BENZODIOXOLE 2,2 DICARBOXYLIC ACID; 5 METHOXY 3 (1,2,3,6 TETRAHYDRO 4 PYRIDYL) 1H INDOLE; 6 [1 (5,6,7,8 TETRAHYDRO 3,5,5,8,8 PENTAMETHYL 2 NAPHTHYL)CYCLOPROPYL]NICOTINIC ACID; 6 CHLORO 2 (1 PIPERAZINYL)PYRAZINE; [[7 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO] 5,6,7,8 TETRAHYDRO 2 NAPHTHYL]OXY]ACETIC ACID ETHYL ESTER; ADRENERGIC RECEPTOR STIMULATING AGENT; AJ 9677; ALPHA ADRENERGIC RECEPTOR STIMULATING AGENT; ANOREXIGENIC AGENT; ANTIDIABETIC AGENT; ANTIHISTAMINIC AGENT; ANTIOBESITY AGENT; AOD 9401; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CP 331679; CYTOKINE; DOPAMINE RECEPTOR STIMULATING AGENT; ENZYME INHIBITOR; ESTRADIOL; FR 165914; GASTROINTESTINAL AGENT; GASTROINTESTINAL POLYPEPTIDE; GLUCOCORTICOID ANTAGONIST; GROWTH HORMONE; L 749372; L 750355; L 755507; LG 100324; LG 100641; LIPID; MPV 1743AIII; N [4 [2 [[2 HYDROXY 3 (4 HYDROXYPHENOXY)PROPYL]AMINO]ETHYL]PHENYL]BENZENESULFONAMIDE; NEUROPEPTIDE; NEUROTRANSMITTER; NITRIC OXIDE SYNTHASE INHIBITOR; OPIATE AGONIST; PHOSPHODIESTERASE INHIBITOR; POLYPHENOL DERIVATIVE; RO 220645; SEROTONIN AGONIST; SIBUTRAMINE; TESTOSTERONE; TETRAHYDROLIPSTATIN; THYROID HORMONE; UL TG 307; UNINDEXED DRUG;

ABDOMINAL DISCOMFORT; APPETITE; BODY WEIGHT; CENTRAL NERVOUS SYSTEM DISEASE; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; DRUG USE; DRUG WITHDRAWAL; ENERGY ABSORPTION; ENERGY EXPENDITURE; ENERGY METABOLISM; FOOD INTAKE; GASTROINTESTINAL DISEASE; GASTROINTESTINAL TRACT FUNCTION; HUMAN; HUNGER; HYPERTENSION; LIPID ABSORPTION; LONG TERM CARE; MALABSORPTION; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NORADRENALIN UPTAKE; OBESITY; PULMONARY HYPERTENSION; REVIEW; RHINITIS; SEROTONIN UPTAKE; TACHYCARDIA; THERMOGENESIS; THYROTOXICOSIS; VALVULAR HEART DISEASE; XEROSTOMIA;

ANTI-OBESITY AGENTS; APPETITE; APPETITE DEPRESSANTS; BODY WEIGHT; ENERGY METABOLISM; HORMONES; HUMANS; INTESTINAL ABSORPTION; OBESITY;

EID: 0038354980     PISSN: 13697056     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (88)

1. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS: Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. J Am Med Assoc (2003) 289(1):76-79.
2. Pérusse L, Bouchard C: Gene-diet interactions in obesity. Am J Clin Nutr (2000) 72(5 Suppl):1285S-1290S.
3. Rolls BJ: The role of energy density in the overconsumption of fat. J Nutr (2000) 130(2 S Suppl):268S-271S.
4. Parham ES: The interaction of eating restraint and stressful life events on women's weight and weight changes. Nutr Res (1990) 10:831-835.
5. Wells JC: Is obesity really due to high energy intake or low energy expenditure? Int J Obesity Relat Metab Disord (1998) 22(11):1139-1140.
6. Hill JO, Wyatt HR: Relapse in obesity treatment: Biology or behavior? Am J Clin Nutr (1999) 69(6):1064-1065.
7. Kolanowski J: Surgical treatment for morbid obesity. Br Med Bull (1997) 53(2):433-444.
8. Atkinson RL: Use of drugs in the treatment of obesity. Annu Rev Nutr (1997) 17:383-403.
9. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature (1994) 372(6505):425-432. This study identified leptin for the first time and proposes it as a potential pondoerostat signal.
10. Campfield LA, Smith FJ, Burn P: Strategies and potential molecular targets for obesity treatment. Science (1998) 280(5368): 1383-1387. Describes obesity-associated gene products and new biochemical pathways and molecular targets for pharmacological intervention.
11. Fernández-López JA, Remesar X, Foz M, Alemany M: Pharmacological approaches for the treatment of obesity. Drugs (2002) 62(6):915-944.
12. Alemany M: Obesidad y nutrición. Alianza Editorial, Grupo Anaya, Madrid, Spain (1992):55-66.
13. Almquist JK, Elias CF, Saper CB: From lesions to leptin: Hypothalamic control of food intake and body weight. Neuron (1999) 22(2):221-232.
14. Garattini S, Samanin R: D-Fenfluramine and salbutamol: Two drugs causing anorexia through different neurochemical mechanisms. Int J Obesity (1984) 8(Suppl 1):151-157.
15. Shaw WN: Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants. Pharmacol Biochem Behav (1993) 46(3):653-659.
16. Tsujii S, Bray GA: Food intake of lean and obese Zucker rats following ventricular infusions of adrenergic agonists. Brain Res (1992) 587(2):226-232.
17. Hagan MM, Moss DE: Suppression of peptide YY-induced hyperphagia by terbutaline. Pharmacol Biochem Behav (1993) 46(3):679-681.
18. Russek M, Vega C, Barrera J, Soto-Mora LM, Lanzagorta A, Racotta R: Anorexia elicited by different catecholamines in rats. Appetite (1987) 9(2):119-126.
19. Halford JC: Pharmacology of appetite suppression: Implication for the treatment of obesity. Curr Drug Targets (2001) 2(4):353-370.
20. Yamada K, Wad E, Santo-Yamada Y, Wada K: Bombesin and its family of peptides: Prospects for the treatment of obesity. Eur J Pharmacol (2002) 440(2-3):281-290.
21. Zelger JL, Carlini EA: Anorexigenic effects of two amines obtained from Catha edulis Forsk (Khat) in rats. Pharmacol Biochem Behav (1980) 12(5):701-705.
22. 1-adrenergic agonist cirazoline on locomotion and brown adipose tissue thermogenesis in the rat. Life Sci (1992) 50(23):1745-1753.
23. Giudicelli JF, Richer C, Berdeaux A: Preliminary assessment of flutiorex, a new anorectic drug, in man. Br J Clin Pharmacol (1976) 3(1):113-121.
24. Yeh SY: Comparative anorectic effect of metaraminol and phenylephrine in rats. Physiol Behav (1999) 68(1-2):227-234.
25. Wellman PJ, Miller J: The effects of phenylpropanolamine on food intake and body weight in the genetically-obese (ob/ob) mouse. Appetite (1987) 9(3):231-236.
26. Greenway FL: Clinical studies with phenylpropanolamine: A metaanalysis. Am J Clin Nutr (1992) 55(1 Suppl):203S-205S.
27. Enzi G, Crepaldi G, Inelmen EM, Bruni R, Baggio B: Efficacy and safety of dexfenfluramine in obese patients. A multicenter study. Clin Neuropharmacol (1988) 11(Suppl 1):S173-S178.
28. McTavish D, Heel RC: Dexfenfluramine: A review of its pharmacological properties and therapeutic potential in obesity. Drugs (1992) 43(5):713-733.
29. Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higgenbottam T, Oakley C, Wouters E, Aubier M, Simonneau G et al: Appetite-suppressant drugs and the rise of primary pulmonary hypertension. N Engl J Med (1996) 335(9):609-616.
30. Li R, Serdula MK, Williamson DF, Bowman BA, Graham DJ, Green L: Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy. Int J Obesity Relat Metab Disord (1999) 23(9):926-928. The unexpected cases of valvulopathy in obese patients forced the withdrawal of dexfenfluramine from the market.
31. Heal DJ, Aspley S, Prow MR, Jackson HC, Martin KF, Cheetam SC: Sibutramine: A novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from D-amphetamine and D-fenfluramine. Int J Obesity Relat Metab Disord (1998) 22(Suppl 1):S18-S28.
32. Finer N: Sibutramine: Its mode of action and efficacy. Int J Obesity Relat Metab Disord (2002) 26(Suppl 4):S29-S33.
33. Bray GA, Blackburn GL, Ferguson JM, Greenway FL, Jain AK, Mendel CM, Mendels J, Ryan DH, Schwartz SL, Scheinbaum ML, Seaton TB: Sibutramine produces dose-related weight loss. Obes Res (1999) 7(2):189-198.
34. Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E: Long-term maintenance of weight loss after a very-low-calorie diet: A randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med (1999) 106(2):179-184.
35. Lean ME: Sibutramine - A review of clinical efficacy. Int J Obesity Relat Metab Disord (1997) 21(Suppl 1):S30-S36.
36. Weintraub M, Rubio A, Golik A, Byrne L, Scheinbaum ML: Sibutramine in weight control: A dose ranging efficacy study. Clin Pharmacol Ther (1991) 50(3):330-337. This study tested the safety and efficacy of two doses of sibutramine (with caloric restriction, behavior modification and exercise) on weight loss during 12 weeks; a significant dose-response relationship was observed.
37. Finer N: Present and future pharmacological approaches. Br Med Bull (1997) 53(2):409-432.
38. Terry P, Gilbert DB, Cooper SJ: Dopamine receptor subtype agonists and feeding behavior. Obes Res (1995) 3(Suppl 4):515S-523S.
39. B receptors on brown fat thermogenesis in the rat. Neuropharmacol (1988) 27(4):363-366.
40. Tsujii S, Bray GA: GABA-related feeding control in genetically-obese rats. Brain Res (1991) 540(1-2):48-54.
41. Cole JL, Leventhal L, Pasternak GW, Bowen WD, Bodnar RJ: Reductions in body weight following chronic central opioid receptor subtype antagonists during development of dietary obesity in rats. Brain Res (1995) 678(1-2):168-176.
42. Cole JL, Berman N, Bodnar RJ: Evaluation of chronic opioid receptor antagonist effects upon weight and intake measures in lean and obese Zucker rats. Peptides (1997) 18(8):1201-1207.
43. Sullivan AC, Gruen RK: Mechanisms of appetite modulation by drugs. Fed Proc (1985) 44(1 Pt 1):139-144.
44. Gibbs J, Young RC, Smith GP: Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol (1973) 84(3):488-495.
45. Tso P, Chen Q, Fujimoto K, Fukagawa K, Sakata T: Apolipoprotein A-IV: A circulating satiety signal produced by the small intestine. Obes Res (1995) 3 (Suppl 5):689S-695S.
46. Hawkins MF: Central nervous system neurotensin and feeding. Physiol Behav (1986) 36(1):1-8.
47. Stein LJ, Woods SC: Gastrin-releasing peptide reduces meal size in rats. Peptides (1982) 3(5):833-835.
48. Merali Z, McIntosh J, Anisman H: Role of bombesin-related peptides in the control of food intake. Neuropeptides (1999) 33(5):376-386.
49. Turton MD, O'Shea D, Gunn I, Beack SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP et al: A role for glucagon-like peptide-1 in the central regulation of feeding. Nature (1996) 379(6560):69-72.
50. Woods SC, Seeley RJ, Porte D Jr, Schwartz MW: Signals that regulate food intake and energy homeostasis. Science (1998) 280(5368):1378-1383.
51. Beck B, Ricky S, Dimitrov T, Stricker-Krongrad A: Opposite regulation of hypothalamic orexin and neuropeptide Y receptors and peptide expressions in obese Zucker rats. Biochem Biophys Res Commun (2001) 286(3):518-523.
52. Jéquier E: Leptin signaling, adiposity, and energy balance. Ann NY Acad Sci (2002) 967:379-388.
53. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannessian JP, Marco CC, McKee LJ, Bauer TL, Caro JF: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med (1996) 334(5):292-295. This paper shows that serum leptin concentrations are correlated with the percentage of body fat, suggesting that obese people are insensitive to endogenous leptin production.
54. Gloaguen I, Costa P, Demartis A, Lazzaro D, Di Marco A, Graziani R, Paonessa G, Chen F, Rosenblum CI, Van Der Ploeg LH , Cortese R et al: Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. Proc Natl Acad Sci USA (1997) 94(12):6456-6461.
55. Siddiqui RA, Williams JF: Tentative identification of the toxohormones of cancer cachexia: Roles of vasopressin, prostaglandin-E2 and cachectin-TNF. Biochem Int (1990) 20(4):787-797.
56. Saghizadeh M, Ong JM, Garvey WT, Henry RR, Kern PA: The expression of TNF-α by human muscle. Relationship to insulin resistance. J Clin Invest (1996) 97(4):1111-1116.
57. Blundell JE, Green SM: Effect of sucrose and sweeteners on appetite and energy intake. Int J Obesity Relat Metab Disord (1996) 20(Suppl 2):S12-S17.
58. Hunt R, Zorich NL, Thomson AB: Overview of olestra: A new fat substitute. Can J Gastroenterol (1998) 12(3):193-197.
59. Comai K, Sullivan AC: Antiobesity activity of pluronic L-101. Int J Obes (1980) 4(1):33-42.
60. Berger M: Pharmacological treatment of obesity. Digestion and absorption inhibitors: Clinical perspective. Am J Clin Nutr (1992) 55(1 Suppl):318S-319S.
61. Puls W, Krause HP, Müller L, Schutt H, Sitt R, Thomas G: Inhibitors of the rate of carbohydrate and lipid absorption by the intestine. Int J Obes (1984) 8(Suppl 1):181-190.
62. Hogan S, Fleury A, Hadvary P, Lengsfeld H, Meier MK, Triscari J, Sullivan AC: Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase. Int J Obes (1987) 11(Suppl 3):35-42.
63. Davidson MH, Hauptman J, Digirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Cheng J, Heymsfield SB: Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: A randomized controlled trial. J Am Med Assoc (1999) 281(3):235-242. This study shows that two-year treatment with orlistat plus diet significantly promotes weight loss, decreases weight regain, and improves some obesity-related disease risk factors.
64. Rösner S, Jöström L, Noack R, Meinders AE, Noseda G: Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res (2000) 8(1):49-61.
65. Scott LJ, Spencer CM: Miglitol: A review of its therapeutic potential in type 2 diabetes mellitus. Drugs (2000) 59(3):521-549.
66. 125I] cyanopindolol. Eur J Pharmacol (1983) 93(3-4):235-243.
67. Collins S, Surwit RS: The β-adrenergic receptors and the control of adipose tissue metabolism and thermogenesis. Recent Prog Horm Res (2001) 56:309-328.
68. 3-adrenoceptor-selective agonists for the treatment of type 2 diabetes and obesity in humans.
69. 3-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr (2002) 76(4):780-788.
70. 3-adrenoceptor in the human heart. J Clin Invest (1996) 98(2):556-562.
71. Bouillaud F, Ricquier D, Thibault J, Weissenbach J: Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein. Proc Natl Acad Sci USA (1985) 82(2):445-448.
72. Ricquier D, Bouillaud F: The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J (2000) 345(Pt 2):161-179.
73. Nedergaard J, Matthias A, Golozoubova V, Jacobsson A, Cannon B: UCP1: The original uncoupling protein- and perhaps the only one? New perspectives on UCP1, UCP2, and UCP3 in the light of the bioenergetics of the UCP1-ablated mice. J Bioenerg Biomembr (1999) 31(5):475-491.
74. Osaka T, Lee TH, Kobayashi A, Inoue S, Kimura S. Thermogenesis mediated by a capsaicin-sensitive area in the ventrolateral medulla. Neuroreport (2000) 11(11):2425-2428.
75. Schwid SR, Hirvonen MD, Keesey RE. Nicotine effects on body weight: A regulatory perspective. Am J Clin Nutr (1992) 55(5):878-884.
76. Oppenheimer JH, Schwartz HL, Lane JT, Thompson MP: Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. J Clin Invest (1991) 87(1):125-132.
77. Bhathena SJ: Relationship between fatty acids and the endocrine system. Biofactors (2000) 13(1-4):35-9.
78. Kim KR, Nam SY, Song YD, Lim SK, Lee HC, Huh KB: Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults. Horm Res (1999) 51(2):78-84.
79. Remesar X, Fernández-López JA, Alemany M: Steroid hormones and the control of body weight. Med Res Rev (1993) 13(5):623-631.
80. Howell S, Shalet S: Testosterone deficiency and replacement. Horm Res (2001) 56(Suppl 1):86-92.
81. Dubuc PU: Effects of estrogen on food intake, body weight, and temperature of male and female obese mice. Proc Soc Exp Biol Med (1985) 18(3):468-473.
82. Adán C, Cabot C, Vil̀a R, Grasa MM, Masanés RM, Esteve M, Estruch J, Fernández-López JA, Remesar X, Alemany M: Oleoyl-estrone treatment affects the ponderostat setting differently in lean and obese Zucker rats. Int J Obesity Relat Metab Disord (1999) 23(4):366-373.
83. Sanchis D, Balada F, Del Mar Grasa M, Virgili J, Peinado J, Monserrat C, Fernández-López JA, Remesar X, Alemany M: Oleoyl-estrone induces the loss of body fat in rats. Int J Obesity Relat Metab Disord (1996) 20(6):588-594.
84. Wright BE, Porter JR, Browne ES, Svec F: Antiglucocorticoid action of dehydroepiandrosterone in young obese Zucker rats. Int J Obesity Relat Metab Disord (1992) 16(8)579-583.
85. Hauner H: The impact of pharmacotherapy on weight management in type 2 diabetes. Int J Obesity Relat Metab Disord (1999) 23(Suppl 7):S12-S17
86. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP: Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science (2000) 288(5475):2379-2381.
87. Levert KL, Waldrop GL, Stephens JM: A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. J Biol Chem (2002) 277(19):16347-1350.
88. Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C: Adipose differentiation-related protein is a ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res (1997) 38(1):2249-2263.