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Journal of Dental Research
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Current Concepts of the Mechanism of Action of Local Anesthetics

Gary R. Strichartz

Department of Physiology & Biophysics, Health Sciences Center, State University of New York, Stony Brook, New York 11794

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.

Journal of Dental Research, Vol. 60, No. 8, 1460-1467 (1981)
DOI: 10.1177/00220345810600080904
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