Relationship Between the 5‐HT3 Receptor Pharmacophore and the Conformations of 5‐Hydroxytryptamine

Abstract

A three-dimensional (3D) pharmacophore for 5-HT3 partial agonists has been developed, using the Catalyst program from a study of 3D structure-activity relationships. The 3D pharmacophore has three chemical features in common with 5-hydroxy-tryptamine (5-HT)—an aromatic ring, a basic centre and a hydrogen-bond-acceptor group. Comparison of 5-HT conformations observed in crystals, and of computed conformations, with the pharmacophore has enabled identification of a biologically active conformation of 5-HT for 5-HT3 receptors, and an extended conformation of 5-HT has been found to agree with the three-dimensional arrangement of the pharmacophoric elements. This conformation of 5-HT might be required for interaction with 5-HT3 receptors in binding sites.