Receptor site topographies for phencyclidine-like and sigma drugs: predictions from quantitative conformational, electrostatic potential, and radioreceptor analyses.
DT Manallack, MG Wong, M Costa, PR Andrews, PM Beart
Mol Pharmacol | Published : 1988
Computer-assisted molecular modelling techniques and electrostatic analyses of a wide range of phenycyclidine (PCP) and sigma ligands, in conjunction with radioreceptor studies, were used to determine the topographies of the PCP and sigma receptors. The PCP receptor model was defined using key molecules from the arylcyclohexylamine, benzomorphan, bridged benz[f]isoquinoline, and dibenzocycloalkenimine drug classes. Hypothetical receptor points (R1, R2) were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor, along with an additional receptor point (R3) representing a hydrogen bond between the nitrogen atom and the receptor. The superim..View full abstract