Conformational analysis and receptor modelling of m1 and m2 selective antagonists

Pharmazie. 1994 Aug;49(8):566-73.

Abstract

On the basis of an elaborate conformational analysis of m1- and m2-selective antagonists a respective pharmacophore was deduced. This then was introduced into models of the two muscarinic receptor subtypes. These models were constructed starting from bacteriorhodopsin as a template in accordance with alignment data and mutation experiments. The validity of the interaction geometries between ligands and receptor subtypes is supported by a significant correlation between calculated interaction energies and experimentally determined affinity data.

MeSH terms

  • Amino Acid Sequence
  • Bacteriorhodopsins / chemistry
  • Computer Graphics
  • Drug Design
  • Humans
  • Ligands
  • Molecular Conformation
  • Molecular Sequence Data
  • Muscarinic Antagonists* / chemical synthesis*
  • Muscarinic Antagonists* / pharmacology
  • Receptors, Muscarinic / chemistry
  • Software

Substances

  • Ligands
  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Bacteriorhodopsins