Enantiomeric N-methyl-4-piperidyl benzilates as muscarinic receptor ligands: Radioligand binding studies and docking studies to models of the three muscarinic receptors M1, M2 and M3 Original Research Article

Benzilic ester derivatives with a basic moiety like N-methyl-4-piperidyl benzilates are potential drugs for the treatment of urinary incontinence, duodenal and gastric ulcers and Parkinson’s disease. The effect of structural variations of chiral N-methyl-4-piperidyl benzilates was investigated using radioligand binding studies on muscarinic receptors (M1–M3). The results of the binding studies demonstrate that the absolute configuration and the aromatic substituent of benzilates have an influence on muscarinic affinity and selectivity. In this regard, (S)-configuration of benzilates and hydrophilic aromatic substituents seems to enhance muscarinic affinity. A model of the receptor ligand complex for N-methyl-4-piperidyl benzilates was obtained by molecular modelling. Both the affinity of enantiomeric benzilic esters and the subtype selectivity for muscarinic receptors are comprehensively explained by this model.