Psychotomimetic drugs as anticholinergic agents. II. Quantum-mechanical study of molecular interaction potentials of 1-cyclohexylpiperidine derivatives with the cholinergic receptor.

Abstract

Molecular structural factors in the interaction of drugs of the phencyclidine series with cholinergic receptors were studied by quantum-mechanical metods. Reactivity criteria were based on an interaction pharmacophore obtained from the electrostatic potential pattern generated in its surroundings by the molecular system. Experimental results referring to the psychotomimetic activity of the drugs and to their anti-acetylcholine properties, established with various peripheral receptors and cholinesterases, were shown to correlate well with the structural requirements obtained from the interaction pharmacophore of acetylcholine. Structural characteristics leading to competitive antagonism are discussed.