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  • Title: Interaction of lidocaine and benzocaine in blocking sodium channels.
    Author: Schmidtmayer J, Ulbricht W.
    Journal: Pflugers Arch; 1980 Aug; 387(1):47-54. PubMed ID: 6251426.
    Abstract:
    1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated in voltage and current clamp experiments at pH 7.2 2. Measured with infrequent test pulses, 0.123 mM lidocaine reduced INa to 54%, 0.25 mM benzocaine to 40% and the mixture 0.125 mM lidocaine +/- 0.25 mM benzocaine to 31% of the control. When hyperpolarizing prepulses (V = -40 mV for 15 ms) preceded the test pulses the respective reductions were to 58%, 74% and 55% i.e. adding benzocaine to lidocaine had little additional effect. 3. Increasing the rate of the prepulse-test pulse pairs from 1 to 20 Hz did not change INa in benzocaine but gradually relieved block by lidocaine; in the mixture this change was much reduced or absent. 4. Switching off prepulses (at 20 Hz) led to a gradual decrease of INa in lidocaine but to a prompt fall in benzocaine and in the mixture. 5. 0.25 mM lidocaine and 0.5 mM benzocaine were approximately equieffective in reducing INa (no prepulse) to 29% and 24%; a one-to-one mixture of the two solutions (0.125 mM lidocaine + 0.25 mM benzocaine) reduced to 27%. 6. In current clamp experiments 0.25 mM lidocaine and 0.36 mM benzocaine reduced the maximum rate of rise of the action potential to 32% and 30%, the mixture of solutions (0.125 mM lidocaine + 0.18 mM benzocaine) to 29%. 7. These results are fully compatible with the idea of a single common binding site for which lidocaine and benzocaine compete.
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