Interaction of lidocaine and benzocaine in blocking sodium channels

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, 0.125 mM lidocaine reduced I_Na 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 I_Na 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 I_Na 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 I_Na (no prepulse) to 29% and 24%; a one-to-one mixture of the twosolutions (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.