Effect of Antazoline on Electrophysiological Properties of Atrial Muscle and Conduction System of the Heart

Abstract

PurposeAntazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline.MethodsAfter successful ablation of supraventricular arrhythmias, the electrophysiological parameters: sinus rhythm cycle length (SRCL), AH, HV, QRS, QT, QTc intervals, Wenckebach point (WP), sinus node recovery period (SNRT), intra- (hRA-CSos) and interatrial conduction time (hRA-CSd), right and left atrium refractory period (RA-; LA-ERP), and atrioventricular node refractory period (AVN-ERP) were assessed initially and after 100, 200, and 300 mg of antazoline given intravenously.ResultsFifteen patients (8 males, 19–72 years old) undergoing EPS and RF ablation were enrolled. After 100 mg bolus, a significant reduction in SRCL was noticed. After antazoline administration, significant prolongation of HV, QRS, QTc, hRA-CSos, hRA-CSd intervals, RA– and LA-ERP and reduction of SRCL were observed. After a total dose of 300 mg, QT interval prolonged significantly. Increasing the dose of antazoline had no impact on AH, Wenckebach point, AVN-ERP, and SNRT.ConclusionAntazoline has an effect on electrophysiological parameters of the atrial muscle and has rapid onset of action. No negative effect on sinus node function and atrioventricular conduction in a unique property among antiarrhythmic drugs.

Clinical effectiveness and safety of antazoline‐based therapy in patients with stable coronary artery disease undergoing pharmacological cardioversion of short‐duration atrial fibrillation in the emergency department

“…5 Basic studies have suggested a multichannel mode of action resulting in, among others, changes in inter-and intraatrial conduction and prolongation of QRS and QT intervals without significant influence on atrio-ventricular node or accessory pathway effective refractory periods. [6][7][8][9] In human healthy volunteers, the terminal elimination half-life of antazoline was 2.29 hours with a mean residence time 3.45 hours. 7 In the same experiment, the antazoline administration resulted in a significant decrease in stroke volume-94.9 ± 21.8 vs 82.4 ± 19.6 mL (P < 0.05).…”

“…Antazoline is a I generation antihistaminic drug with antifibrillatory properties . Basic studies have suggested a multichannel mode of action resulting in, among others, changes in inter‐ and intraatrial conduction and prolongation of QRS and QT intervals without significant influence on atrio‐ventricular node or accessory pathway effective refractory periods . In human healthy volunteers, the terminal elimination half‐life of antazoline was 2.29 hours with a mean residence time 3.45 hours .…”

Intravenous antazoline, a first‐generation antihistaminic drug with antiarrhythmic properties, is a suitable agent for pharmacological cardioversion of atrial fibrillation induced during pulmonary vein isolation due to the lack of influence on atrio‐venous conduction and high clinical effectiveness (AntaEP Study)

“…Antazoline is a I generation antihistaminic drug displaying antiarrhythmic properties . Antazoline is administered intravenously in 50–100 mg boluses until conversion of AF to sinus occurs or up to a cumulative dose of 250–300 mg . In a single clinical study over healthy volunteers, after the injection of 100 mg of antazoline the drug concentration in plasma declined rapidly to 10% of baseline within half an hour.…”

“…The detailed mechanism of antiarrhythmic properties of antazoline is not entirely clear but current data point to a multichannel mode of action involving sodium and potassium channels . Animal model studies report a significant increase of atrial and ventricular effective refractory periods (ERP) leading to a remarkable increase in atrial and ventricular postrepolarization refractoriness, an antiarrhythmic mechanism observed in amiodarone or quinidine …”

“…In a recent study of patients scheduled for ablation of supraventricular tachycardia, antazoline was shown to influence a series of electrophysiological parameters, including the prolongation of interatrial conduction and left atrium ERP. Similarly to the previous study, there was an increase in QTc duration and no significant change in systolic or diastolic blood pressure …”