5-HT(4) receptors: history, molecular pharmacology and brain functions.
Twenty years ago, we started the characterization of a 5-HT receptor coupled to cAMP production in neurons. This receptor obviously had a different pharmacology to the other 5-HT receptors described at that time, i.e. the 5-HT(1), 5-HT(2), 5-HT(3) receptors. We proposed to name it the 5-HT(4) receptor. Nowadays, 5-HT(4) receptors are one of the most studied GPCRs belonging to the "rhodopsin" family. Thanks to the existence of a great variety of ligands with inverse agonist, partial agonist, agonist and antagonist profiles, the pharmacological and physiological properties of this receptor are beginning to emerge. Although some 5-HT(4) partial agonists have been on the market for gastro-intestinal pathologies, 5-HT(4) receptor drugs have still to be commercialized for brain disorders. However, since 5-HT(4) receptors have recognized effects on memory, depression and feeding in animal models, there is still hope for a therapeutic destiny of this interesting target in brain disorders.
Bockaert
Joël
J
CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France. joel.bockaert@igf.cnrs.fr
Claeysen
Sylvie
S
Compan
Valérie
V
Dumuis
Aline
A
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008958:Models, Molecular; D011985:Receptors, Serotonin / Q000235:genetics / Q000266:history / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*
D011985:Receptors, Serotonin; D018490:Serotonin Agents; D000242:Cyclic AMP