Abstract

Various phenyl, cycloalkyl and alkyl substituted β-hydroxybutyric acid esters of 2-diethylaminoethanol have cholinolytic action comparable to that of the corresponding hydroxyacetate esters.

The most effective compounds, within a variety of structurally diverse esters, have a hydroxyl group at a distance of 4-7 Å from the amine group. The replacement of the hydroxyl by a hydrogen atom greatly reduces cholinolytic potency in most instances.

The various effective substitutions of the carbon atoms near the hydroxyl provide an umbrella-like mass which may form a protecting shield over the receptor surface thereby preventing close approach of stimulating molecules such as acetylcholine. The data suggest that other effects also may be important and that these groups may in some specific way increase affinity for the receptor site.

Quaternization of the amine to form the methyl-or ethylhalide salts increases cholinolytic potency and toxicity. This is similar to the increase in cholinomimetic potency and toxicity which is associated with methylhalide quaternization of various tertiary amines and may result, in part, from an increased reactivity of the cationic group.