Effects of o-Methyl Substitution on the Pharmacological Properties of 1,1-Dimethyl-4-phenylpiperazinium

Abstract

THE potent nicotine-like ganglion stimulant action of choline aryl ethers (Me₃N⁺CH₂CH₂OAr X−)¹ is known to depend on the molecule's ability to adopt a conformation in which the aryl ring, ether oxygen and β-carbon atom are in the same plane². This planarity would be favoured by overlap between the aromatic π electrons and an unshared pair of 2p electrons on the ether oxygen. In some substituted derivatives, however, steric hindrance prohibits such a conformation and the nicotinic stimulant properties are lost. Thus, although both choline phenyl ether and choline o-tolyl ether are potent ganglion stimulants³, choline 2,6-xylyl ether (xylocholine), in which the aryl ring lies in a plane perpendicular to that of the Ar—O—C bonds⁴, has no such activity⁵.