5-HT4 Receptor Antagonists: Structure-Affinity Relationships and Ligand- Receptor Interactions

Among serotonin receptors (5-HTRs), the 5-HT4 subtype is of considerable interest because it is involved in (patho)physiological processes both in peripheral and central nervous systems. In addition to the clinical use of 5-HT4R agonists in the treatment of gastrointestinal motility disorders, the potential use of antagonists in the treatment of irritable bowel syndrome, arrhythmias and micturition disturbances are currently under investigation. This article will review the development of the most important classes of 5- HT4R antagonists with an emphasis on benzimidazole derivatives, their structure-affinity relationships, ligand-receptor interactions and pharmacological applications.