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Targeting 5-HT receptors for the treatment of obesity

Authors
Journal
Current Opinion in Pharmacology
1471-4892
Publisher
Elsevier
Publication Date
Volume
11
Issue
1
Identifiers
DOI: 10.1016/j.coph.2011.01.005

Abstract

Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT 1B, 5-HT 2C and 5-HT 6. Hypophagic effects are elicited through agonism of the former two receptors, whereas antagonism of the 5-HT 6 receptor appears to have an anorectic effect. All three targets have been validated through extensive studies including knockout mice and selective ligand assessment. 5-HT 1B receptor agonists have limited utility due to mechanism-based side effects, whereas 5-HT 2C receptor agonists suffer from challenges associated with selectivity over the closely related 5-HT 2A and 5-HT 2B receptors. 5-HT 6 receptor antagonists appear to offer great promise, although the mechanisms through which they reduce food intake and body weight are not fully understood.

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