Vanoxerine, a new drug for terminating atrial fibrillation and flutter.

Abstract

BACKGROUND:

Vanoxerine produces potent block of cardiac hERG, sodium, and L-type calcium channels. Block is strongly frequency dependent, is unassociated with transmural dispersion of repolarization, and occurs at concentrations safe in humans. Therefore, we proposed that vanoxerine might be antiarrhythmic. In these studies, we tested the hypothesis that vanoxerine would terminate induced atrial fibrillation (AF) and atrial flutter (AFL) in dogs with sterile pericarditis (SP).

METHODS AND RESULTS:

In 9 SP dogs, 11 episodes each of sustained (>10 minutes) AF and AFL were induced. Electrophysiological studies were performed before and after infusion of vanoxerine, which effectively terminated AF and AFL in 19 of 22 episodes. Simultaneous multisite mapping during 3 AF and 3 AFL episodes demonstrated that termination of each arrhythmia occurred with termination of the driver (a reentrant circuit) following an increase in tachycardia CL. Except for conduction in an area of slow conduction in the driver's reentrant circuit, vanoxerine did not significantly affect intraatrial or atrioventricular conduction time, QRS duration, or QT/QTc intervals. Ventricular refractoriness prolonged minimally during ventricular pacing at 400 and 333 ms (176 +/- 16 ms to 182 +/- 16 ms; 173 +/- 11 ms to 178 +/- 18 ms, respectively). Vanoxerine minimally increased (mean 0.7 mA) atrial stimulus threshold for capture.

CONCLUSIONS:

Vanoxerine effectively terminated induced, sustained AF and AFL in the canine SP model, and produced insignificant or minimal changes in refractoriness, conduction time, or stimulus threshold, consistent with little proarrhythmic risk.

• Authors: Naomichi Matsumoto, Celeen M Khrestian, Kyungmoo Ryu, Antonio E Lacerda, Arthur M Brown, Albert L Waldo
• Journal: Journal of cardiovascular electrophysiology (J Cardiovasc Electrophysiol) Vol. 21 Issue 3 Pg. 311-9 (Mar 2010) ISSN: 1540-8167 [Electronic] United States
• PMID: 19817929 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Asthmatic Agents
• Piperazines
• vanoxerine

Topics

• Animals
• Anti-Asthmatic Agents (administration & dosage)
• Atrial Fibrillation (diagnosis, drug therapy, physiopathology)
• Atrial Flutter (diagnosis, drug therapy, physiopathology)
• Dogs
• Electrocardiography (drug effects)
• Heart Rate (radiation effects)
• Piperazines (administration & dosage)
• Treatment Outcome