Positively active: how local anesthetics work.

The action of local anesthetics, containing a tertiary nitrogen, on mammalian nonmyelinated fibers of the rabbit’s vagus nerve has been analyzed 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 in which it had been blocked by pretreatment with a local anesthetic, by increasing the pH of the perfusing solution from approximately 7.0 to 9.5; block was rapidly reestablished when the fibers were again perfused with the solution of pH approximately 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