Antiarrhythmic vs. antifibrillatory activity of the basic diphenylhydantoin derivative 3-[3-(4-phenyl-1-piperidyl)propyl]-5-(4-methoxyphenyl)-5-phenylhydantoin hydrochloride.
The effects of 3-[3-(4-phenyl-1-piperidyl)propyl]-5-(4-methoxyphenyl)-5-phenylhydantoin hydrochloride (TR 2985), a basic diphenylhydantoin derivative, were studied in four canine models of experimental cardiac dysrhythmias. In conscious dogs, 48 h after myocardial infarction, TR 2985 significantly reduced the frequency of spontaneous ventricular arrhythmias. However, in anesthetized dogs, TR 2985 produced only a slight and insignificant increase in the ventricular fibrillation threshold. In conscious dogs, 4 to 7 days after myocardial infarction, TR 2985 failed to prevent the electrical induction of reentrant ventricular tachycardia, and failed to protect against the development of ventricular fibrillation in response to ischemia at a site distant from the previous infarction. These results indicate that TR 2985 may be effective in preventing arrhythmias of a non-reentrant nature, but may be relatively ineffective in preventing reentrant ventricular tachycardia or ventricular fibrillation.
Lynch
J
J
Montgomery
D
D
Ventura
A
A
Wilber
D
D
Lucchesi
B R
BR
D000768:Anesthesia, General; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D010672:Phenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013610:Tachycardia / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D010672:Phenytoin; C024222:ropitoin hydrochloride