COMPUTER-ASSISTED ANALYSIS OF HISTAMINE H-2-RECEPTOR AND H-3-RECEPTORAGONISTS

Using molecular modelling methods the structural and conformational re quirements for receptor affinity and activity of histamine H-2- and H- 3-receptor agonists have been investigated. Two pharmacophore models w ere derived which indicate the different sterical requirements for the two histamine receptor subtypes. On the basis of these results we sug gest that histamine may interact in different bioactive conformations with the corresponding receptor subtypes. Subsequent investigations of the molecular interaction potentials support the described orientatio ns and conformations of H-2- and H-3-agonists. The derived pharmacopho re models together with the molecular interaction patterns of the agon ists may serve as basis for amino acid models of the binding regions o f H-2- and H-3-receptor sites.