Receptor regulatory properties evident in the molecular similarity of serotonin receptor ligands and purine nucleotides

Previous computational studies have explored the relative molecular similarity inherent in the ligands of neurotransmitter‐regulated cell receptors and purine nucleotides. This study presents the results of an investigation of the major serotonin (5‐HT) receptor classes, using molecular superimposition and fitting data. Ligands for 5HT1B/C/D and 5HT4/7 receptors identified pharmacophores in the adenine ring of ATP. 5‐HT2 and 5‐HT3 receptor ligands identified pharmacophores in the guanosine nucleotide and cyclic nucleotide, respectively. The described molecular similarity is consistent with the cyclic nucleotide responses observed during signal transduction events initiated by 5‐HT, and the reported similarity between ligands of the 5‐HT1B and 5‐HT1D, 5‐HT1A and 5‐HT7, and 5‐HT4 and 5‐HT3 receptors. The results are discussed in terms of current pharmacophoric models and signal transduction events involving interaction between G‐protein receptors and catalytic sites.