Targeting 5-HT receptors for the treatment of obesity

Curr Opin Pharmacol. 2011 Feb;11(1):52-8. doi: 10.1016/j.coph.2011.01.005. Epub 2011 Feb 15.

Abstract

Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT(1B), 5-HT(2C) and 5-HT(6). Hypophagic effects are elicited through agonism of the former two receptors, whereas antagonism of the 5-HT(6) receptor appears to have an anorectic effect. All three targets have been validated through extensive studies including knockout mice and selective ligand assessment. 5-HT(1B) receptor agonists have limited utility due to mechanism-based side effects, whereas 5-HT(2C) receptor agonists suffer from challenges associated with selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. 5-HT(6) receptor antagonists appear to offer great promise, although the mechanisms through which they reduce food intake and body weight are not fully understood.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Molecular Targeted Therapy
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology*
  • Serotonin Antagonists / therapeutic use*
  • Serotonin Receptor Agonists / pharmacology*
  • Serotonin Receptor Agonists / therapeutic use*

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin