COCAINE CONCENTRATION-EFFECT RELATIONSHIP IN THE PRESENCE AND ABSENCEOF LIDOCAINE - EVIDENCE OF COMPETITIVE-BINDING BETWEEN COCAINE AND LIDOCAINE

To better understand the interaction between cocaine and lidocaine, we studied the cocaine's concentration-effect relationship for action po tential duration (APD) and the rate of rise of phase 0 of the action p otential (V-max) of canine papillary muscle in the presence and absenc e of lidocaine. We measured APD and V-max during programmed stimulatio n and superfusion with normal Tyrode's, 30 mu M cocaine and 30 mu M co caine + 30 mu M lidocaine. Using two microelectrodes, we simultaneousl y recorded action potentials from two sites during programmed stimulat ion and measured the conduction velocity and effective refractory peri od during exposure to normal Tyrode's, cocaine and cocaine + lidocaine . Cocaine with or without lidocaine delayed the plateau of the APD res titution curve. At 1000 msec cycle length, the addition of 30 mu M lid ocaine to the superfusate containing 30 mu M cocaine shortened the tim e constant for reactivation of V-max from 514 +/- 63 to 234 +/- 28 mse c (P < .01). Lidocaine also improved the conduction velocity decreased by cocaine, but did not significantly change the effective refractory period. The configuration of cocaine concentration-effect curve for A PD was biphasic. For cocaine concentrations < 100 mu M, APD progressiv ely prolonged with increasing concentrations. As cocaine concentration s increased > 100 mu M, APD progressively shortened. The addition of l idocaine to the superfusate with cocaine > 100 mu M tended to attenuat e the progressive APD shortening due to cocaine. Lidocaine shifted the curve correlating cocaine concentration and reduction of V-max rightw ard, but preserved E(max) at cocaine concentration > 225 mu M. These f indings suggest competitive antagonism between cocaine and lidocaine a t a single sodium channel receptor. Conclusion: lidocaine displaces co caine from the sodium channel receptor through competitive binding. Li docaine may prove to be beneficial in reversing cocaine-induced slowin g of ventricular conduction.