5-HT1 Receptors

Laurence      Lanfumey; Michel      Hamon

doi:10.2174/1568007043482570

Abstract

Among the seven classes of serotonin (5-hydroxytryptamine, 5-HT) receptorswhich have been identified to date, the 5-HT1 class is comprised of five receptor types,with the 5-HT1A, 5-HT1B and 5-HT1Dcharacterized by a high affinity for 5-carboxamidotryptamine,the 5-HT1E and 5-HT1F characterized by a low affinity for this syntheticagonist, and all five having a nanomolar affinity for the endogenous indolamine ligand.The genes encoding 5-HT1 receptors have been cloned in both human and rodents,allowing the demonstration that they all belong to the G-protein-coupled receptor superfamilywith the characteristic7hydrophobic(transmembrane) domain-containing amino acid sequence. All the5-HT1 receptor types actually interact with Gαi / Gαoproteins to inhibit adenylyl cyclase and modulate ioniceffectors, i.e. potassium and / or calcium channels. Probes derived from the knowledge of amino acid sequence ofthe receptor proteins and of nucleotide sequence of their encoding mRNAs allowed the mapping of all the 5-HT1 receptor types in the central nervous system and other tissues. For the last twenty years, bothpharmacological investigations with selective agonists and antagonists and phenotypical characterization ofknock-out mice have been especially informative regarding the physiological implications of 5-HT1 receptortypes. This research ends notably with the development of triptans, whose agonist activity at 5-HT1B, 5-HT1Dand 5-HT1F receptors underlies their remarkable efficacy as antimigraine drugs. Clear-cut evidence of theimplication of 5-HT1 receptors in anxiety- and depression-like behaviours and cognitive performances inrodents should hopefully promote research toward development of novel drugs with therapeutic potential inpsychopathological and dementia-related diseases.

Keywords: 5-HT1B, bothpharmacological, anxiety