5-HT4 receptors

Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):39-51. doi: 10.2174/1568007043482615.


Serotonin 4 receptors (5-HT(4)Rs) were discovered 15 years ago. They are coded by a very complex gene (700Kb, 38 exons) which generates eight carboxy-terminal variants (a, b, c, d, e, f, g, n). Their sequences differ after position L(358). Another variant is characterized by a 14 residue insertion within the extracellular loop 2. Highly selective potent 5-HT(4) receptor antagonists and partial agonists which cross the blood-brain barrier have been synthesized, but a specific full agonist for brain studies is still missing. Based on physiological and behavioral experiments, 5-HT(4)Rs may be targets to treat cognitive deficits, abdominal pain and feeding disorders. One 5-HT(4)R-directed drug (SL65.0155) is already in phase II to treat patients suffering from memory deficits or dementia.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / physiopathology
  • Cloning, Molecular
  • Digestive System / drug effects
  • Digestive System / metabolism
  • Drug Evaluation / methods
  • GTP-Binding Proteins / metabolism
  • Gastrointestinal Diseases / drug therapy*
  • Gastrointestinal Diseases / physiopathology
  • Humans
  • Immunohistochemistry
  • Receptors, Serotonin, 5-HT4 / classification*
  • Receptors, Serotonin, 5-HT4 / drug effects*
  • Receptors, Serotonin, 5-HT4 / genetics
  • Receptors, Serotonin, 5-HT4 / metabolism
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Signal Transduction
  • Structure-Activity Relationship
  • Tissue Distribution


  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptors, Serotonin, 5-HT4
  • GTP-Binding Proteins