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1 Department of Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico; Department of Physiology and Pharmacology, Duke University Medical Center, Durham, North Carolina
The hypothesis concerning the active form and the site of action of tertiary amine local anesthetics (Narahashi et al., 1970) predicts that there should be certain quaternary compounds capable of blocking action potentials only from inside the nerve membrane. A quaternary compound, hemicholinium-3, and two quaternary derivatives of lidocaine, QX-314 and QX-572, have been found to block the action potential of squid giant axons much more effectively from the inside of the nerve membrane than from the outside. The blocking potency of the internally applied quaternary compounds was independent of pH changes in either internal or external solutions. Neither choline nor acetylcholine, when applied inside, had any effect on the action potential or any protective action against the blockage caused by hemicholinium-3. Therefore, the blockage by hemicholinium-3 is not due to the lack of choline. The results strongly support the hypothesis that local anesthetics block the action potential from inside the nerve membrane in charged forms.
Submitted on February 19, 1969
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