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

Abstract

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.

Voltage-gated Na+ channel ligands and ATP: relative molecular similarity and implications for channel function

“…This study investigates relative molecular similarity within the structures of ATP and drugs with recognised VGNC blocking action, with the aim of further clarifying their modulatory role on Na + -channel function. The rationale for the study is provided by the aforementioned regulatory effects of ATP on VGNC function and evidence of drug receptor pharmacophores within purine nucleotide structures (Williams et al 2004). Several atomic groups in the adenine ring system relate to the described anticonvulsant and local anaesthetic motifs and these require further investigation.…”