The Comparative Antiarrhythmic Actions of Lidocaine and its Quarternary Derivative, Methyl Lidocaine
Lidocaine has proved to be an effective antiarrhythmic agent in the management of ventricular arrhythmias subsequent to acute myocardial infarction. Lidocaine's short duration of action and its propensity for producing central nervous system (CNS) stimulation suggest that a safer and more effective therapeutic agent, based on a modification of the lidocaine structure, might be found. The quaternary ammonium compound, methyl lidocaine, was synthesized and its actions in experimentally-induced arrhythmias were studied and compared to those of lidocaine. The antiarrhythmic effects of lidocaine and methyl lidocaine were examined in the anesthetized dog against ouabain-induced ventricular tachycardia and in conscious animals with ventricular tachycardia 48 hours after two-stage ligation of the anterior descending coronary artery. Both pharmacological agents were capable of reversing digitalis-induced arrhythmias and restoring normal sinus rhythm in animals 48 hours after surgical ligation of the anterior descending coronary artery, but methyl lidocaine remained effective for a significantly longer period and its continual administration was not associated with signs of CNS toxicity. In experiments designed to determine the electrical fibrillation threshold, both drugs were able to reduce the vulnerability to ventricular fibrillation but the time course of action for each drug differed. Lidocaine had an immediate effect of increasing the ventricular fibrillation threshold whereas the peak effect of methyl lidocaine was delayed and the increase in the fibrillation threshold lasted longer. This study concludes that the quaternary derivative of lidocaine, methyl lidocaine, possesses antiarrhythmic properties similar to those of lidocaine, but differs in its duration of action and lack of overt stimulatory effects upon the central nervous system.
- Coronary artery ligation
- Central nervous system toxicity
- Quaternary ammonium compound
- Fibrillation threshold
- Received May 11, 1973.
- Accepted August 30, 1973.
- © 1974 American Heart Association, Inc.