In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS‐7229

Preclinical Research 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 QT cb were lengthened by both compounds; however, higher doses of E ‐7229 resulted in shortening of the prolonged QT and QT cb . Ventricular effective refractory period ( VERP ) was significantly prolonged by either drug studied. Threshold doses to produce QT 50% , QT max , VERP 50% , and VERP max 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.