Document Detail

Melanocortin receptors as targets in the treatment of obesity.
MedLine Citation:
PMID:  17584129     Owner:  NLM     Status:  MEDLINE    
The central melanocortin system plays a critical role in energy homeostasis. It is well established that melanocortin-containing neurons are nutritionally regulated and that genetic alterations in the melanocortin system produce profound effects on food intake, energy expenditure, and body weight. Within the brain, melanocortin-producing neurons originate in the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the solitary tract (NTS) in the brainstem and project to various nuclei modulating energy balance. A large body of pharmacological and genetic evidence implicates the central melanocortin 4 receptors (MC4Rs) in the effects of melanocortin peptides on ingestive behaviour, energy expenditure, and body weight. Preclinical studies with endogenous and synthetic melanocortin ligands demonstrate that they produce potent effects on food intake and energy expenditure. Clinical studies thus far have been somewhat less successful and have been hampered by the induction of side effects, which present obstacles to the development of successful therapeutic agents. However, various promising strategies are being pursued to overcome these limitations, including the synthesis of more selective and potent melanocortin analogs.
Daniel D Lam; I Sadaf Farooqi; Lora K Heisler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current topics in medicinal chemistry     Volume:  7     ISSN:  1873-4294     ISO Abbreviation:  Curr Top Med Chem     Publication Date:  2007  
Date Detail:
Created Date:  2007-06-22     Completed Date:  2007-09-24     Revised Date:  2010-09-20    
Medline Journal Info:
Nlm Unique ID:  101119673     Medline TA:  Curr Top Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1085-1097     Citation Subset:  IM    
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
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MeSH Terms
Drug Design
Melanocortins / metabolism
Obesity / drug therapy*,  metabolism*,  pathology
Receptors, Melanocortin / agonists,  metabolism*
Signal Transduction
Grant Support
068086//Wellcome Trust; //Wellcome Trust
Reg. No./Substance:
0/Melanocortins; 0/Receptors, Melanocortin

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