ON THE ACTIVE STRUCTURE OF LOCAL ANESTHETICS

¹ Department of Pharmacology, Albert Einstein College of Medicine, Yeshiva University, New York, N. Y., and the Department of Biochemistry, Geigy Research Laboratories, Ardsley, N. Y.

The action of local anesthetics, containing a tertiary nitrogen, on mammalian nonmyelinated fibers of the rabbit's vagus nerve has been analyzed in order to determine whether the uncharged or the positively charged form of these compounds is responsible for their ability to block impulse conduction.

The compounds studied were dibucaine, tetracaine, chlorpromazine, imipramine and procaine.

Impulse conduction was restored, in fibers where it had been blocked by pretreatment with a local anesthetic, by increasing the pH of the perfusing solution from about 7.0 to about 9.5; block was rapidly re-established when the fibers were again perfused with the solution of pH about 7.0.

From the way in which the size of the action potential varied with pH in nerve fibers pretreated with a local anesthetic it has been concluded that the active form of the local anesthetic is the cation.

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