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 5HT(1B/C/D) and 5HT(4/7) receptors identified pharmacophores in the adenine ring of ATP. 5-HT(2) and 5-HT(3) 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-HT(1B) and 5-HT(1D), 5-HT(1A) and 5-HT(7), and 5-HT(4) and 5-HT(3) receptors. The results are discussed in terms of current pharmacophoric models and signal transduction events involving interaction between G-protein receptors and catalytic sites.