Funding: This study was supported by the Hungarian National Office for Research and Technology (NKFP_07-A2-2008-0260; GOP-1.1.2-07/1-2008-0004; TÁMOP-4.2.2.-08/1-2008-0014, OM-00174/2008; TÁMOP-4.2.2/B-10/1-2010-0024; GOP-1.1.1-07/1-2008-0032 and GOP-1.2.1-08-2009-0023) and the Hungarian Scientific Research Fund (OTKA-75965). The project is cofinanced by the European Union and the European Social Fund.
In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS-7229
Article first published online: 28 DEC 2012
© 2012 Wiley Periodicals, Inc.
Drug Development Research
Volume 74, Issue 3, pages 173–185, May 2013
How to Cite
Drimba, L., Nemeth, J., Sári, R., Di, Y., Kovács, A., Szénási, G., Szilvássy, Z. and Peitl, B. (2013), In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS-7229. Drug Dev. Res., 74: 173–185. doi: 10.1002/ddr.21058
The authors declare no conflicts of interest.
- Issue published online: 10 APR 2013
- Article first published online: 28 DEC 2012
- Manuscript Accepted: 5 DEC 2012
- Manuscript Received: 1 NOV 2012
- Hungarian National Office for Research and Technology. Grant Numbers: NKFP_07-A2-2008-0260, GOP-1.1.2-07/1-2008-0004, TÁMOP-4.2.2.-08/1-2008-0014, OM-00174/2008, TÁMOP-4.2.2/B-10/1-2010-0024, GOP-1.1.1-07/1-2008-0032, GOP-1.2.1-08-2009-0023
- Hungarian Scientific Research Fund. Grant Number: OTKA-75965
- European Union and the European Social Fund
- cardiac arrhythmias;
- preclinical drug development;
- cardiovascular safety;
- preclinical model
The basic hemodynamic, electrophysiological, and pharmacological effects of EGIS-7229 (E-7229) were evaluated and compared with those of a pure “Class III“ antiarrhythmic drug (GLG-V-13) in conscious rabbits. Both compounds decreased heart rate dose-dependently. Mean arterial blood pressure was not influenced by E-7229; however, GLG-V-13 produced a significant elevation on this parameter. Left ventricular end-diastolic pressure was gradually increased by E-7229, while GLG-V-13 induced more considerable elevation on that at intermediate doses. QT and QTcb were lengthened by both compounds; however, higher doses of E-7229 resulted in shortening of the prolonged QT and QTcb. Ventricular effective refractory period (VERP) was significantly prolonged by either drug studied. Threshold doses to produce QT50%, QTmax, VERP50%, and VERPmax were significantly higher for E-7229 compared with GLG-V-13. Significantly higher doses were required for E-7229 to induce arrhythmias. The safety ratio was comparable for both of the compounds. E-7229 can exert multiple actions on cardiac ion channels with minimal influence on hemodynamic parameters and reduced proarrhytmic profile in our preclinical model.