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Journal of Pharmacology And Experimental Therapeutics, Vol. 157, Issue 2, 388-405, 1967
Copyright © 1967 by American Society for Pharmacology and Experimental Therapeutics

ACTION OF LOCAL ANESTHETICS ON COUPLING SYSTEMS IN MUSCLE

C. Paul Bianchi 1 and T. C. Bolton 1

1 Department of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Lidocaine, in contrast to procaine and tetracaine, does not inhibit the caffeine-induced contracture at pH 7.20 nor the associated calcium influx and efflux; instead, lidocaine potentiates the initial phase of the caffeine contracture. The potentiation of the caffeine contracture appears to depend upon the uncharged form of the local anesthetics. The tertiary amine local anesthetics are capable of inducing contractures in striated muscle when the intracellular ratio of the charged to uncharged form is of the order of 1.25:1 but not when the ratio is 4:1. It is proposed that the charged and uncharged forms of the local anesthetic act in a synergistic manner at the excitable surface membrane to block the action potential but act antagonistically at the membrane of the sarcoplasmic reticulum and the t-tubule with respect to excitation-contraction coupling in muscle.

Submitted on January 3, 1966
Accepted on March 9, 1967




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Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics.