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Curr Top Med Chem. 2002 Jun;2(6):625-41.

5-HT(4) receptor antagonists: structure-affinity relationships and ligand-receptor interactions.

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Departamento de Química Orgánica I, Facultad de Ciencias Qu micas, Universidad Complutense, E-28040 Madrid, Spain.


Among serotonin receptors (5-HTRs), the 5-HT(4) 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-HT(4R) 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-HT(4R) antagonists with an emphasis on benzimidazole derivatives, their structure-affinity relationships, ligand-receptor interactions and pharmacological applications.

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