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

Computational studies have revealed similarities in the relative configurations of purine nucleotides and ligands for histamine, acetylcholine and adrenergic receptors. In common with other G‐protein‐regulated receptors, dopamine receptors are associated with specific changes in nucleotide levels during signal transduction processes. The purpose of this study was to investigate molecular similarity in dopamine receptor ligands and purine nucleotides. Molecular superimposition and fitting data for D1‐like receptor ligands identified a pharmacophore in the adenine and ribose rings of ATP. D2‐like agonists and antagonists related to a pharmacophore in the guanine and ribose rings of GTP. The results are consistent with the hypothesis that the dopamine receptor family may have evolved from receptors for the ATP and GTP nucleotides.