5-HT4 receptors

Joël Bockaert (1) , S. Claeysen (1) , Valerie Compan (1) , Aline Dumuis (1)

1 CCIPE - Centre CNRS-INSERM de Pharmacologie Endocrinologie

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.

Mots clés: splice variants; G proteins; neurotransmitter release; cognition; pain; 5-HT4 receptors; CNS drug targets; anxiety; feeding

Domaines: Neurobiologie; Pharmacologie

Joël Bockaert, S. Claeysen, Valerie Compan, Aline Dumuis. 5-HT4 receptors. Current Drug Targets -CNS and Neurological Disorders-, 2004, 3 (1), pp.39-51. ⟨10.2174/1568007043482615⟩. ⟨hal-01667891⟩