5-HT4 Receptors

J      Bockaert; S      Claeysen; V      Compan; A      Dumuis

Abstract

Serotonin 4 receptors (5-HT4Rs) were discovered 15 years ago. They are codedby a very complex gene (700Kb, 38 exons) which generates eight carboxy-terminalvariants (a, b, c, d, e, f, g, n). Their sequences differ after position L358. Another variant ischaracterized by a 14 residue insertion within the extracellular loop 2. Highly selectivepotent 5-HT4 receptor antagonists and partial agonists which cross the blood-brain barrier have been synthesized, but a specific full agonist for brain studiesis still missing. Based on physiological and behavioral experiments, 5-HT4Rs may be targets to treatcognitive deficits, abdominal pain and feeding disorders. One 5-HT4R-directed drug(SL65.0155) is already in phase II to treat patients suffering from memory deficits ordementia.

Keywords: 5-ht4 receptors, splice variants, g proteins, neurotransmitter release, cognition, pain, anxiety, feeding, cns drug targets