Melanocortin receptors as targets in the treatment of obesity.

Abstract

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.

• Authors: Daniel D Lam, I Sadaf Farooqi, Lora K Heisler
• Journal: Current topics in medicinal chemistry (Curr Top Med Chem) Vol. 7 Issue 11 Pg. 1085-1097 ( 2007) ISSN: 1873-4294 [Electronic] United Arab Emirates
• PMID: 17584129 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Melanocortins
• Receptors, Melanocortin

Topics

• Animals
• Drug Design
• Humans
• Melanocortins (metabolism)
• Obesity (drug therapy, metabolism, pathology)
• Receptors, Melanocortin (agonists, metabolism)
• Signal Transduction