Antiarrhythmic properties of benzyl-triamterene derivatives in the coronary artery ligated and reperfused rat.
Triamterene (CAS 396-01-0) and a series of benzyl-triamterene derivatives were evaluated for their antiarrhythmic properties in the coronary artery ligated and reperfused (CAL-R) rat. The effects were compared with the antiarrhythmic activity of the potassium sparing diuretic amiloride and drugs out of the class-I (lidocaine) and class-III (amiodarone and sotalol). Triamterene and sotalol revealed at high doses antifibrillator activity, while the benzyl-triamterenes 2, 3, 5 and 6 could also depress ventricular extrasystoles (VES) and ventricular tachycardia (VT). At low doses the most benzyltriamterenes protected significantly against ventricular fibrillation (VF) and so they were equieffective or more effective than amiodarone or lidocaine. Amiloride showed in the CAL-R rat no antiarrhythmic activity, so that we conclude different mechanisms responsible for antikaliuretic and antiarrhythmic properties of amiloride and triamterenes. Taking into account the results of recently reported in vitro studies, where we could demonstrate antiarrhythmic activity combined with positive inotropic properties for triamterenes, the antiarrhythmic profile of these compounds may offer new possibilities for the treatment of ventricular arrhythmias.
Busch
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AE
Faculty of Biochemistry, Pharmacy and Food Chemistry, Department of Pharmacology, University of Frankfurt/Main, Fed. Rep. of Germany.
Netzer
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T
Ullrich
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F
Mutschler
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E
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014223:Triamterene / Q000031:analogs & derivatives* / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D014223:Triamterene