Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 68, Issue 6, Pages 852-860Publisher
WILEY
DOI: 10.1111/j.1365-2125.2009.03550.x
Keywords
5-HT2c; MCH1; neuropeptides; obesity; sibutramine; weight loss agents
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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.
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