DEVELOPMENT OF A BINDING-SITE MODEL FOR HISTAMINE H-3-RECEPTOR AGONISTS

On the basis of molecular modelling studies the structural and conform ational requirements for receptor affinity and activity of histamine H -3-receptor agonists were studied. It was shown that the known H-3-rec eptor agonists can be fitted accurately into a common pharmacophoric p attern. Using the YAK pseudoreceptor approach an amino acid model for the H-3-receptor agonist binding site was generated which reflects bin ding properties and biological data of the investigated agonists. The postulated binding site model was validated by predicting biological d ata for four structures not considered in model construction. The amin o acid positions of the pseudoreceptor were found to be in good agreem ent with calculated GRID interaction fields for the investigated hista mine H-3-receptor agonists.