Multiple Serotonin Receptors: Opportunities for New Treatments for Obesity?

Recent progress in the molecular pharmacology of 5-HT receptors and the development of selective ligands for various 5-HT receptor subtypes has advanced our understanding of the role of 5-HT mechanisms in the control of food intake and bodyweight. The most intensively investigated 5-HT receptor subtypes have been the 5-HT1A receptor, the 5-HT1B receptor and the 5-HT2C receptor. The overall pattern of results to date suggests that selective 5-HT2C agonists may be novel anorectic drugs and prove useful in the treatment of obesity. However, a number of issues remain unresolved, particularly regarding potential side-effects, as the 5-HT2C receptor agonist mCPP has been reported to induce anxiety and nausea in humans, actions that would clearly limit its therapeutic utility. In addition, the possible role of recently cloned 5-HT receptor subtypes such as 5-ht5, 5-ht6 and 5-ht7, remains unexplored and the development of selective ligands for these sites has the potential to lead to new treatments for obesity.