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Serotonergic Anti-Obesity Agents

Past Experience and Future Prospects

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Abstract

The role of serotonin (5-hydroxytryptamine) in appetite control is long established. Serotonergic manipulations reduce food intake in rodents in a manner consistent with satiety. In humans, drugs such as fenfluramine, dexfenfluramine and sibutramine all reduce energy intake, suppress hunger and enhance satiety. Effects on eating behaviour and subjective sensations of appetite are associated with the weight loss-inducing effects of these treatments. Currently, no appetite-suppressing drugs are approved specifically for the treatment of obesity. However, a new generation of serotonergic drugs have progressed through clinical development. The serotonin 5-HT2C− receptor selective agonist lorcaserin, a drug specifically developed to target satiety without producing the side effect profiles of its predecessors, has been shown to significantly reduce energy intake and body weight. The weight loss produced by lorcaserin appears modest, and behavioural effects, particularly its supposed satiety-enhancing effects, have yet to be characterized. The monoaminergic re-uptake inhibitor tesofensine has also been shown to produce impressive weight loss in smaller-scale clinical studies. It remains unclear if this drug produces any effects on appetite mediated by serotonin, or whether weight loss is produced largely through enhanced energy expenditure. Evidence indicates that tesofensine strengthens satiety, but behavioural specificity and psychological side effects remain an issue. The serotonergic system remains a viable target for anti-obesity treatment. In this review, we examine the limited behavioural data available on these two new CNS-acting appetite suppressants.

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Acknowledgements

No sources of funding were used in the preparation of this article. Dr Halford declares associations with the following companies/organizations: Coca-Cola, Danone, Eli Lilly, GlaxoSmithKline, Prosidion and OSI Pharmaceuticals. Dr Lawton declares an association with Arla Foods Kellogg’s, National Starch, Royal FrieslandCampina and Welch Foods Inc. Professor Blundell declares associations with Amylin, Barilla, Coca-Cola, Covance, Danone, Kraft Foods, Kellogg’s, Mars, Merck, National Starch, Orexigen Therapeutics and Unilever. Dr Harrold declares association with the California Prune Board and National Starch. Dr Boyland has no conflicts of interest that are directly relevant to the content of this article.

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  1. Experimental Psychology, University of Liverpool, Eleanor Rathbone Building, Bedford Street South, Liverpool, L69 7ZA, UK

    Jason C. G. Halford, Emma J. Boyland & Joanne A. Harrold

  2. Institute of Psychological Sciences, University of Leeds, Leeds, UK

    Clare L. Lawton & John E. Blundell

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  1. Jason C. G. Halford
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Correspondence to Jason C. G. Halford.

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Halford, J.C.G., Boyland, E.J., Lawton, C.L. et al. Serotonergic Anti-Obesity Agents. Drugs 71, 2247–2255 (2011). https://doi.org/10.2165/11596680-000000000-00000

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