Pharmacological targeting of the serotonergic system for the treatment of obesity

J Physiol. 2009 Jan 15;587(1):49-60. doi: 10.1113/jphysiol.2008.164152. Epub 2008 Nov 24.


The attenuation of food intake as induced by an increase in serotonergic (5-hydroxytryptamine, 5-HT) efficacy has been a target of antiobesity pharmacotherapies. However, the induction of tolerance and/or side-effects limited the clinical utility of the earliest serotonin-related medications. With the global prevalence of obesity rising, there has been renewed interest in the manipulation of the serotonergic system as a point of pharmacological intervention. The serotonin(2C) receptor (5-HT(2C)R), serotonin(1B) (rodent)/serotonin(1Dbeta) (human) receptor (5-HT(1B/1Dbeta)R) and serotonin(6) receptor (5-HT(6)R) represent the most promising serotonin receptor therapeutic targets. Canonical serotonin receptor compounds have given way to a myriad of novel receptor-selective ligands, many of which have observable anorectic effects. Here we review serotonergic compounds reducing ingestive behaviour and discuss their clinical potential for the treatment of obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Appetite Regulation / drug effects
  • Appetite Regulation / physiology
  • Eating / drug effects
  • Eating / physiology
  • Fenfluramine / pharmacology
  • Humans
  • Hypothalamus / drug effects
  • Hypothalamus / physiopathology
  • Mice
  • Mice, Knockout
  • Models, Neurological
  • Obesity / drug therapy*
  • Obesity / physiopathology*
  • Receptors, Serotonin / deficiency
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Serotonin / physiology*
  • Serotonin Agents / pharmacology*


  • Receptors, Serotonin
  • Serotonin Agents
  • Fenfluramine
  • Serotonin