5-hydroxytryptamine medications for the treatment of obesity

J Neuroendocrinol. 2015 Jun;27(6):389-98. doi: 10.1111/jne.12287.


The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15 years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2 C R as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2 C R agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2 C R modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2 C R agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.

Keywords: 5-HT2CR; lorcaserin; obesity; serotonin; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Appetite / drug effects
  • Biological Availability
  • Energy Metabolism
  • Humans
  • Obesity / drug therapy*
  • Pro-Opiomelanocortin / physiology
  • Serotonin / physiology
  • Serotonin 5-HT2 Receptor Agonists / pharmacokinetics
  • Serotonin 5-HT2 Receptor Agonists / pharmacology
  • Serotonin 5-HT2 Receptor Agonists / therapeutic use*


  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin
  • Pro-Opiomelanocortin