New central targets for the treatment of obesity
Article first published online: 22 SEP 2009
© 2009 AMRI. Journal compilation © 2009 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 68, Issue 6, pages 852–860, December 2009
How to Cite
Sargent, B. J. and Moore, N. A. (2009), New central targets for the treatment of obesity. British Journal of Clinical Pharmacology, 68: 852–860. doi: 10.1111/j.1365-2125.2009.03550.x
- Issue published online: 27 NOV 2009
- Article first published online: 22 SEP 2009
- Received 13 March 2009 Accepted15 September 2009
- weight loss agents
The review focuses on the central neuronal circuits involved in energy homeostasis and the opportunities these offer for pharmacological intervention to decrease feeding behaviour and reduce weight. This article is based on the presentation ‘New central targets for the treatment of obesity’ (Sargent, British Pharmacological society, Clinical Section Symposium, December 2008).
Central neuronal substrates controlling weight offer numerous opportunities for pharmacological intervention. These opportunities range from non-specific enhancement of monoamine signalling (triple reuptake inhibitors) to targeting specific monoamine receptor subtypes (5-HT2c and 5-HT6). The data reviewed suggest that these approaches will lead to weight loss; whether this is sufficient to produce clinically meaningful effect remains to be determined. Combination therapy targeting more than one mechanism may be a means of increasing the magnitude of the response. Preclinical studies also suggest that novel approaches targeting specific neuronal pathways within the hypothalamus, e.g. MCH1 receptor antagonism, offer an opportunity for weight reduction. However, these approaches are at an early stage and clinical studies will be needed to determine if these novel approaches lead to clinically meaningful weight loss and improvements in co-morbid conditions such as diabetes and cardiovascular disorders.