Further aspects of stereospecificity in interaction of polyfunctional amine derivatives with biological receptors

Abstract

Isomers of the quaternary amine salt muscarine, and their acetate derivatives, have been studied as weak-to-moderate inhibitors of the in vitro acetylcholinesterase-acetylcholine system. The results are interpreted in terms of 3-point binding of each inhibitor species to the catalytic surface, in accordance with the pharmacologic findings of Waser on the cholinergic receptor. Acetylation increases the inhibitory power of a given muscarine isomer by a factor of about 2.6, but the acetates are not hydrolyzed in the presence of the esterase. Additional evidence pointing to the stereospecificity of biological receptors at the enzymic and intact animal levels of complexity has been obtained with the quaternized o-chlorophenylacetate esters of tropine and ψ-tropine, and with some heterocyclic amines. The specificity patterns determined with acetylcholinesterase responses do not parallel those with receptor systems in intact animals.