title: Central and peripheral molecular targets for antiobesity pharmacotherapy.
abstract: Obesity has emerged as one of the principal worldwide health concerns of the modern era, and there exists a tremendous unmet clinical need for safe and effective therapies to combat this global pandemic. The prevalence of obesity and its associated comorbidities, including cardiovascular and metabolic diseases, has focused the attention of those in drug discovery and development on generating effective modalities for the treatment and prevention of obesity. Early efforts in the field of obesity pharmacotherapy centered on the development of agents with indeterminate mechanisms of action. This led to treatment paradigms characterized by significant off-target effects. In the past two decades, new insights have been made into the physiologic regulation of energy balance and the subordinate central and peripheral circuits coordinating appetite, metabolism, and lipogenesis. These studies have revealed previously unrecognized molecular targets for controlling appetite and managing weight from which has emerged a new wave of targeted pharmacotherapies to prevent and control obesity.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Valentino
authors.forename: J E
authors.initials: JE
authors.lastname: Lin
authors.forename: S A
authors.initials: SA
authors.lastname: Waldman
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001067:Appetite Depressants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D001067:Appetite Depressants
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13226-31
references.pmid: 16891413
references.citation: Obesity (Silver Spring). 2009 Jan;17(1):30-9
references.pmid: 18997675
references.citation: J Clin Endocrinol Metab. 2003 Aug;88(8):3989-92
references.pmid: 12915697
references.citation: J Clin Endocrinol Metab. 2007 May;92(5):1754-7
references.pmid: 17341568
references.citation: Regul Pept. 1996 Sep 16;65(3):165-74
references.pmid: 8897639
references.citation: Br J Clin Pharmacol. 2009 Dec;68(6):861-74
references.pmid: 20002080
references.citation: Curr Ther Res Clin Exp. 1972 Aug;14(8):525-39
references.pmid: 4629314
references.citation: Gastroenterology. 2005 Nov;129(5):1430-6
references.pmid: 16285944
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10750-5
references.pmid: 18669668
references.citation: Cell Metab. 2009 Jan 7;9(1):35-51
references.pmid: 19117545
references.citation: Endocrinology. 2004 Jun;145(6):2687-95
references.pmid: 15001546
references.citation: N Engl J Med. 2000 Dec 21;343(25):1833-8
references.pmid: 11117974
references.citation: Am J Med. 1981 Nov;71(5):887-90
references.pmid: 7304660
references.citation: Pharmacol Rev. 2007 Jun;59(2):151-84
references.pmid: 17540905
references.citation: Obes Res. 2003 Feb;11(2):170-5
references.pmid: 12582210
references.citation: N Engl J Med. 2000 Dec 21;343(25):1826-32
references.pmid: 11117973
references.citation: Drug Discov Today. 2009 May;14(9-10):509-15
references.pmid: 19429511
references.citation: Neuropsychopharmacology. 2007 Apr;32(4):822-34
references.pmid: 16841072
references.citation: Gastroenterology. 2002 Oct;123(4):1120-8
references.pmid: 12360474
references.citation: N Engl J Med. 1997 Aug 28;337(9):581-8
references.pmid: 9271479
references.citation: Cor Vasa. 1985;27(2-3):160-71
references.pmid: 3928246
references.citation: Br J Clin Pharmacol. 2009 Dec;68(6):852-60
references.pmid: 20002079
references.citation: Cell Metab. 2006 Oct;4(4):275-82
references.pmid: 17011500
references.citation: Int J Obes (Lond). 2006 Dec;30(12):1729-36
references.pmid: 16619056
references.citation: Eur J Pharmacol. 2004 Mar 8;487(1-3):183-97
references.pmid: 15033391
references.citation: Am Fam Physician. 2004 Nov 1;70(9):1731-8
references.pmid: 15554492
references.citation: Proc Natl Acad Sci U S A. 2008 May 20;105(20):7257-62
references.pmid: 18458326
references.citation: Metabolism. 2003 Dec;52(12):1638-42
references.pmid: 14669170
references.citation: Int J Obes (Lond). 2005 Nov;29(11):1308-14
references.pmid: 15953938
references.citation: Endocrinology. 2009 Jun;150(6):2526-30
references.pmid: 19372201
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10730-5
references.pmid: 12149466
references.citation: Gen Pharmacol. 1988;19(2):201-4
references.pmid: 3127269