5-HT4 receptors

• Published in: Current drug targets. CNS & neurological disorders Vol. 3; no. 1; p. 39
• Main Authors: Bockaert, J, Claeysen, S, Compan, V, Dumuis, A
• Format: Journal Article
• Language: English
• Published: Netherlands 01.02.2004
• Subjects: 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; Gastrointestinal Diseases - drug therapy; Gastrointestinal Diseases - physiopathology; GTP-Binding Proteins - metabolism; 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
• ISSN: 1568-007X
• 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.