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

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.