Configuration and Anesthetic Activity of Aromatic Alcohols. ∗

Abstract

In general, local anesthetics are deficient in duration of action rather than potency. A striking demonstration of prolongation of effect as a result of a small change in structure of a drug-compound has recently been afforded. It is definitely established in the sympathomimetic amines that the transformation of the side chain so that the carbon bearing the nitrogen becomes a secondary carbon atom results in prolongation of effect. 1 To test the validity of this principle in another field, we are now studying for local anesthetic activity some derivatives of ephedrine in which the same peculiarity of structure exists. Of other series, procaine type compounds do not readily lend themselves for this study because of the difficulty of preparing the desired amino-alcohols. However, the aromatic alcohols with pertinent structure are easily obtained. Some of these have been studied before; in fact it has been stated, 2 on rather invalid evidence, that the change from primary to secondary to tertiary alcohol reduces the activity.

Anesthesia of the rabbit cornea and the frog sciatic nerve has been determined for a series of primary, secondary, and tertiary alcohols, all of which were redistilled before use. The results from local application of aqueous solutions at the concentrations noted are seen in the table in which the figures indicate average duration of anesthesia in minutes for the cornea in 3 different rabbits for each drug, and average time in minutes for the production of sensory block of the sciatic nerve in at least 4 different frogs in each instance. Tests were made at minute intervals and the respective findings usually agreed within 2 minutes. The data indicate the relative merits of the compounds both with regard to duration of anesthesia and speed with which it may be induced.