CONFORMATIONAL-ANALYSIS AND RECEPTOR MODELING OF M1 AND M2 SELECTIVE ANTAGONISTS

On the basis of an elaborate conformational analysis of m1- and m2-sel ective antagonists a respective pharmacophore was deduced. This then w as introduced into models of the two muscarinic receptor subtypes. The se models were constructued starting from bacteriorhodopsin as a templ ate in accordance with alignment data and mutation experiments. The va lidity of the interaction geometries between ligands and receptor subt ypes is supported by a significant correlation between calculated inte raction energies and experimentally determined affinity data.