title: Antiarrhythmic properties of triamterene derivatives in the coronary artery ligated rat model.
abstract: Triamterene and several triamterene derivatives were tested for antiarrhythmic activity in the coronary artery ligated and reperfused (CAL-R) rat. The class-III antiarrhythmic drugs (+/-)-sotalol and amiodarone, the class-I antiarrhythmics lidocaine and quinidine as well as the potassium sparing diuretic amiloride were used as reference drugs. Triamterene at the highest dose (30 mumol/kg) revealed a 100% protection against ventricular fibrillation (VF), whereas at 10 mumol/kg no antiarrhythmic activity for triamterene could be found. For compound 4 (10 mumol/kg) a 75% protection against VF could be demonstrated, while 2, 3, and 5 revealed only a 25% protection. Compared to the reference drugs, triamterene and the derivatives 2-5 are more potent than (+/-)-sotalol, but less potent than lidocaine, quinidine and amiodarone. For amiloride as well as for the potent potassium retaining triamterene derivative 6 no antiarrhythmic activity could be shown. Therefore, we conclude different mechanisms responsible for the potassium sparing and antiarrhythmic properties of triamterene and its derivatives.
authors.affiliation: Faculty of Biochemistry, Pharmacy and Food Chemistry, Department of Pharmacology, University of Frankfurt/Main, Federal Republic of Germany.
authors.forename: A E
authors.initials: AE
authors.lastname: Busch
authors.forename: F
authors.initials: F
authors.lastname: Ullrich
authors.forename: E
authors.initials: E
authors.lastname: Mutschler
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014223:Triamterene / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D011188:Potassium; D014223:Triamterene