REVERSAL OF THE ELECTROCARDIOGRAPHIC EFFECTS OF COCAINE BY LIDOCAINE .1. COMPARISON WITH SODIUM-BICARBONATE AND QUINIDINE

Based on modulated receptor concepts, an agent with fast on-off sodium channel binding properties (e.g., lidocaine) may reverse the effects of a drug with slow on-off kinetics (e.g., cocaine) through competitio n for a single receptor site on the sodium channel. We compared the ef fects of two drugs with different sodium channel-binding kinetics with those of sodium bicarbonate, a known antidote, on cocaine-induced slo wing of ventricular conduction. Electrocardiographic (ECG) intervals w ere recorded before and after the addition of cocaine 30 muM in 26 iso lated, Tyrode-perfused guinea pig hearts. The effects of the three pot ential antidotes were then analyzed: equimolar lidocaine (8 hearts), e quimolar quinidine (6), and sodium bicarbonate (8). Cocaine significan tly increased all ECG intervals. The addition of lidocaine to cocaine- containing perfusate decreased QRS duration from 42 +/- 3 to 29 +/- 3 msec (p<0.01), a 60% reversal. Addition of sodium bicarbonate to incre ase the pH of the perfusate from 7.37 +/- 0.09 to 7.52 +/- 0.08 (p<0.0 1) decreased the QRS duration from 38 +/- 4 to 30 +/- 6 msec (p<0.01), a 47% reversal. Addition of quinidine 30 muM augmented the effects of cocaine: QRS increased from 40 +/- 6 msec to 54 +/- 9 msec (p<0.01). Consistent with modulated receptor concepts, lidocaine reverses slowed ventricular conduction due to cocaine. The magnitude of this reversal is similar to that due to sodium bicarbonate. The potential of fast o n-off agents to serve as antidotes for cocaine-induced arrhythmias req uires further study.