5-HT1 receptors

Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):1-10. doi: 10.2174/1568007043482570.

Abstract

Among the seven classes of serotonin (5-hydroxytryptamine, 5-HT) receptors which have been identified to date, the 5-HT(1) class is comprised of five receptor types, with the 5-HT(1A), 5-HT(1B) and 5-HT(1D) characterized by a high affinity for 5-carboxamido-tryptamine, the 5-HT(1E) and 5-HT(1F) characterized by a low affinity for this synthetic agonist, and all five having a nanomolar affinity for the endogenous indolamine ligand. The genes encoding 5-HT(1) receptors have been cloned in both human and rodents, allowing the demonstration that they all belong to the G-protein-coupled receptor super-family with the characteristic 7 hydrophobic (transmembrane) domain-containing amino acid sequence. All the 5-HT(1) receptor types actually interact with G alpha i/G alpha o proteins to inhibit adenylyl cyclase and modulate ionic effectors, i.e. potassium and/or calcium channels. Probes derived from the knowledge of amino acid sequence of the receptor proteins and of nucleotide sequence of their encoding mRNAs allowed the mapping of all the 5-HT(1) receptor types in the central nervous system and other tissues. For the last twenty years, both pharmacological investigations with selective agonists and antagonists and phenotypical characterization of knock-out mice have been especially informative regarding the physiological implications of 5-HT(1) receptor types. This research ends notably with the development of triptans, whose agonist activity at 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptors underlies their remarkable efficacy as antimigraine drugs. Clear-cut evidence of the implication of 5-HT(1) receptors in anxiety- and depression-like behaviours and cognitive performances in rodents should hopefully promote research toward development of novel drugs with therapeutic potential in psychopathological and dementia-related diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cloning, Molecular
  • Drug Evaluation / methods
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / metabolism*
  • Receptors, Serotonin, 5-HT1 / classification*
  • Receptors, Serotonin, 5-HT1 / drug effects*
  • Receptors, Serotonin, 5-HT1 / genetics
  • Receptors, Serotonin, 5-HT1 / metabolism
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Signal Transduction
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Receptor Agonists