, Volume 67, Issue 1, pp 27–56 | Cite as

Serotonergic Drugs

Effects on Appetite Expression and Use for the Treatment of Obesity
  • Jason C. G. Halford
  • Joanne A. Harrold
  • Emma J. Boyland
  • Clare L. Lawton
  • John E. Blundell
Review Article


Over 35 years of research suggests that endogenous hypothalamic serotonin (5-hydroxytryptamine) plays an important part in within-meal satiation and post-meal satiety processes. Thus, the serotonin system has provided a viable target for weight control, critical to the action of at least two effective anti-obesity treatments, both producing clinically significant weight loss over a year or more. Numerous serotonin receptor subtypes have been identified; of these, serotonin 5-HT1B and 5-HT2C receptors have been specifically recognised as mediators of serotonin-induced satiety.

A number of serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), dexfenfluramine and 5-HT2C receptor agonists, have been shown to significantly attenuate rodent bodyweight gain. This effect is strongly associated with marked hypophagia and is probably mediated by the hypothalamic melanocortin system. Additionally, sibutramine, dexfenfluramine, fluoxetine and the 5-HT2C receptor agonist chlorophenylpiperazine (mCPP) have all been shown to modify appetite in both lean and obese humans, resulting in reduced caloric intake. Clinical studies demonstrate serotonergic drugs specifically reduce appetite prior to and following the consumption of fixed caloric loads, and cause a reduction in pre-meal appetite and caloric intake at ad libitum meals. Weight loss in the obese has also been produced by treatment with both the serotonin precursor 5-hydroxytryptophan and the preferential 5-HT2C receptor agonist mCPP.

A new generation of 5-HT2C receptor selective agonists have been developed and at least one, lorcaserin (APD356), is currently undergoing clinical trials. In addition, 5-HT6 receptor antagonists such as PRX-07034 and BVT74316 have been shown to potently reduce food intake and bodyweight gain in rodent models and have recently entered clinical trials. However, the role of the 5-HT6 receptor in the expression of appetite remains to be determined. The hope is that these drugs will not only be free of their predecessors’ adverse effect profiles, but will also be equally or more effective at regulating appetite and controlling bodyweight.



The authors would like to thank Miss Lisa D.M. Richards for her help in preparing this manuscript and Dr Steve Vickers (RenaSci Consultancy Ltd) for providing much useful material for inclusion within this review. The authors would like in particular to thank Lora Heisler (University of Cambridge), Joel Elmquist (Harvard Medical School) and Michael Cowley (Oregon Health Sciences University) for providing updates on their most recent research and allowing us to reproduce their figure. The website for the Kissileff Laboratory is http://www.liv.ac.uk/Psychology/kissilefflab/Home.html.

The laboratory would like to thank corporate donors GlaxoSmithKline, NJ, USA, for providing funds for postgraduate training. Drs Harrold and Halford have received research funding from Predix Pharmaceuticals. Professor Blundell and Dr Halford have received research funding from Sanofi-Aventis.


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Jason C. G. Halford
    • 1
    • 2
  • Joanne A. Harrold
    • 1
    • 3
  • Emma J. Boyland
    • 1
  • Clare L. Lawton
    • 2
  • John E. Blundell
    • 2
  1. 1.Kissileff Laboratory for the Study of Human Ingestive Behaviour, School of PsychologyUniversity of LiverpoolLiverpoolUK
  2. 2.Institute of PsychologyUniversity of LeedsLeedsUK
  3. 3.Department of Medicine, Diabetes and Endocrinology Research GroupUniversity of LiverpoolLiverpoolUK

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