The inhibitory activity of 36 structurally related quaternary ammonium compounds was undertaken as a logical extension of our earlier report studying the discrete nature of the anionic receptor of a typical cholinergic receptor, acetylcholinesterase. The results permit some sophistication in the discussion of the several mechanisms apparently operative in this system. N A 4~ earlier report (1) the authors postulated I that the inhihition of acctylcholinesterase (AChE) by simple quatcrnary ammonium compounds could be ascertained as a function of affinity for the enzyme and that certain relationships existed between the ionic volume of the inhibitory ion and its affinity for the enzyme.Our results prompted a logical extension of the compounds under evaluation in order to clarify the role of ion volume in affinity for a cholinergic receptor.To meet this end 36 quaternary ammonium compounds were prepared and examined enzymologically. The compounds were : Walkyltrimethylammoniums, A-alkyltriethylammoniums, and N-alkylquinuclidiniums, where the alkyl group was varied from methyl through decyl plus isopropyl; tetrapropylammonium; tetrabutylammonium; and tetrapentylammoniuin. These compounds include 3 homologous series, many of which have been examined in other cholinergic systems. Several interesting related compounds are included such as the isopropyl derivatives and the tetraalkyl derivatives. The conforinational uniqueness of the quinuclidinium Compounds was discussed in a n earlier paper (1).The fundamental rationale for studying competitive inhibition of AChE in a study of the receptor site was similarly established in the first report.EXPERIMENTAL Chemistry salts are givcn in Table I. Properties and recrystallization solvents for allReceived December 1, 1965. from the