Journal of Dental Research, Vol 60, 1460-1470, Copyright © 1981 by International & American Associations for Dental Research Online Journals
Current concepts of the mechanism of action of local anesthetics
G. R. Strichartz
Recent experiments are reviewed to present a current view of the mechanisms
of conduction block by local anesthetics. Local anesthetics block the
sodium channels whose opening causes the rising phase of the action
potential. Both charged and neutral forms of local anesthetics are able to
block channels. Charged anesthetics interfere with a "gating" mechanism
after gaining access to a "receptor" site in the aqueous pore of the
channel from the axoplasmic surface of the membrane. This site is only
available to charged compounds when the gate of the channel is open. In
contrast, uncharged compounds (including the free base form of local
anesthetics) appear to reach the site through the membrane's lipid
interior, bypassing the channel "gates." Anesthetics blocking the gate of
the channel can either enhance or inhibit the normal inactivation mechanism
of the sodium channel, depending on the particular anesthetic.
