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In vivo assessment of class III agents and their antiarrhythmic activity
Author(s) -
Gibson J. K.,
Kersten J. A.
Publication year - 1990
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.430190207
Subject(s) - disopyramide , in vivo , sotalol , pharmacology , repolarization , medicine , antiarrhythmic agent , cardiology , mechanism of action , electrophysiology , chemistry , biology , in vitro , heart disease , atrial fibrillation , biochemistry , microbiology and biotechnology
Abstract A variety of in vivo models have been used to detect and develop novel antiarrhythmic/antifibrillatory agents. However, most of these models primarily have identified the class I agents that block sodium ion currents during the upstroke of the cardiac action potential. Since we are interested in identifying agents with a class III electrophysiologic action, i.e. delayed repolarization of the cardiac action potential, we have focused our drug discovery process on a specific, somewhat uncommon in vivo canine model. These studies have demonstrated that class I agents such as encainide, disopyramide, or U58797, a novel benzamide, are clearly identified in the ouabain‐toxic dog or the postinfarction (24–48 hr) conscious dog. In contrast, class III agents such as clofilium sotalol are identified in an acute canine model of coronary artery occlusion and reperfusion. This occlusion‐reperfusion model allows us to further identify the antiarrhythmic and antifibrillatroy actions of novel class III agents.