Antiarrhythmic and antifibrillatory properties of McN-4130 in several animal models.
McN-4130 is an experimental compound having antiarrhythmic and antifibrillatory activity in several animal models. In anesthetized, open-chest pigs subjected to total occlusion and subsequent reperfusion of the left anterior descending coronary artery, McN-4130 dose-dependently (2.5-10.0 mg/kg i.v.) protected against fibrillation and death. Mean arterial pressure was not significantly affected, but heart rate was dose-dependently reduced. In anesthetized normal dogs, McN-4130 increased ventricular fibrillation threshold for up to 45 min. This increase in fibrillation threshold was associated with concurrent increases in ventricular conduction time and ventricular effective refractory period. In conscious dogs subjected to occlusion of the left anterior descending coronary artery 24 h previously, McN-4130, 2.5 and 5.0 mg/kg i.v., significantly reduced the rate of ventricular arrhythmias for up to 45 min. McN-4130 was more effective and had a longer duration of action than comparable doses of lidocaine and disopyramide. McN-4130 was orally effective in this model at 10 mg/kg. These results indicate that McN-4130, a structurally unique experimental antiarrhythmic compound, may be useful as a ventricular antiarrhythmic agent with antifibrillatory properties.
Damiano
B P
BP
Department of Biological Research, McNeil Pharmaceutical, Spring House, Pennsylvania 19477.
Sit
S P
SP
Fortunato
M A
MA
Stranieri
M T
MT
Brannan
M D
MD
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D007211:Indoles; C054575:McN 4130