The pharmacological action of some ethers and esters of saligenin. 1

Abstract

Benzyl alcohol saligenin and other aromatic alcohols have been shown to possess local anesthetic and antispasmodic action (Macht; Hirschfelder; Hjort). Hirschfelder and Quigley have also demonstrated that the local anesthetic action of benzyl alcohol and its derivatives is diminished when one of the inactive hydrogens (i.e., in the CH₂ of the CH₂OH carbinol group) is substituted by another radical; or, in other words, that the secondary aromatic alcohols are not as good local anesthetics as the primary, and that substitutions for both the CH₂ hydrogens (tertiary alcohols) causes complete loss of local anesthetic action.

Although Hirschfelder, Lundholm and Norrgard had demonstrated that methyl and ethyl substitutions on the phenolic hydroxyl of saligenin rendered the substances more irritating than saligenin, a more extensive study of this type of substitution products was desirable, particularly on account of the fact that they furnished some alcohols homologous with acetyl-salicylic acid.

The substances studied may be devided into three groups:

I. Ethers of saligenin with substitution on the phenolic hydroxyl : i.e., the ethyl, n-butyl, iso-amyl and benzyl ethers.

II. Esters of saligenin with substitution on the phenolic hydroxyl (acetyl and monobenzoyl saligenin).

III. An ester with substitution on both hydroxyls (dibenzoyl saligenin).

All of these esters and ethers except the dibenzoyl compound are oily liquids, and the latter is a solid; and all are practically insoluble in water but soluble in the usual organic solvents and in olive oil. Their pharmacological properties were therefore studied by dissolving the substances in olive oil and emulsifying this with acacia by the Continental method.

Toxicity tests, made by determining the dose which was lethal for frogs in twenty-four hours, gave the following results: For the ethers, ethyl saligenin 0.5 mg. per gram frog, n-butyl 0.25 mg., iso-amyl 0.12, benzyl 0.36 to 4 mg.; for the esters, acetyl saligenin 0.9 mg., benzoyl 1 .o mg., dibenzoyl 2.0 to 3.0 mg. All of these compounds are therefore more toxic than saligenin itself.