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In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS ‐7229
Author(s) -
Drimba László,
Nemeth Jozsef,
Sári Réka,
Di Yin,
Kovács Anikó,
Szénási Gábor,
Szilvássy Zoltán,
Peitl Barna
Publication year - 2013
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21058
Subject(s) - in vivo , medicine , hemodynamics , blood pressure , pharmacology , heart rate , diastole , cardiology , qt interval , biology , microbiology and biotechnology
Preclinical ResearchThe 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.