Computer‐Assisted Analysis of Histamine H2− and H3‐Receptor Agonists

Using molecular modelling methods the structural and conformational requirements for receptor affinity and activity of histamine H2- and H3-receptor agonists have been investigated. Two pharmacophore models were derived which indicate the different sterical requirements for the two histamine receptor subtypes. On the basis of these results we suggest that histamine may interact in different bioactive conformations with the corresponding receptor subtypes. Subsequent investigations of the molecular interaction potentials support the described orientations and conformations of H2- and H3-agonists. The derived pharmacophore models together with the molecular interaction patterns of the agonists may serve as basis for amino acid models of the binding regions of H2- and H3-receptor sites.