Interactions of aryl esters in the tropine and ψ-tropine series with tissue chemoreceptors. The ortho effect. VII

Abstract

Studies on toxic properties of substituted phenylacetic esters in the tropine and ψ-tropine amino alcohol series have revealed a subtle “ortho effect” in ester-chemoreceptor interactions. Receptors in the isolated rat phrenic nerve-diaphragm preparation and at the catalytic locus on acetylcholinesterase are quite sensitive to tropine vs. ψ-tropine configurations in esters bearing ortho, meta, or para substituents on the phenyl nucleus. In contrast, receptors mediating convulsive death in the mouse are fully as sensitive to ring stereochemistry in esters bearing m- or p-substituents, but lose their ability to discriminate between topine and ψ-tropine structure when the phenyl group is substituted in ortho position. This latter finding is independent of the electronic character of the substituent in ortho position, but appears to be related to a requirement for a certain minimum steric bulk of that substituent. These results are interpreted in terms of possible modes of attachment of the aryl esters to central and peripheral chemoreceptor surfaces.