title: QT-prolonging class I drug, disopyramide, does not aggravate but suppresses adrenaline-induced arrhythmias. Comparison with cibenzoline and pilsicainide.
abstract: We investigated the effects of class I antiarrhythmic drugs on corrected QT (QTc) interval and adrenaline-induced arrhythmias in halothane-anaesthetized, closed-chest dogs. For this purpose, we plotted a dose-response curve for adrenaline by calculating the arrhythmic ratio, which is the number of ventricular ectopic beats induced by adrenaline divided by the total heart rate, and observed the changes in the arrhythmic ratio-adrenaline dose relation before and after administration of class I drugs. Disopyramide and cibenzoline decreased the arrhythmic ratio induced by adrenaline. Disopyramide prolonged the QTc interval by 20% (P<0.01), but cibenzoline did not. Pilsicainide prolonged the QTc interval (12%), but this drug did not change the arrhythmic ratio. These results indicate that in contrast to the class III drugs which we have reported earlier, i.e. 1, 3-dimethyl-6-2-[N-(2-hydroxyethyl)-3-(4-nitrophenyl)-propylamino]eth ylamino-2,4 (1H,3H)-pyrimidinedione hydrochloride (MS-551), 1-(2-amino-4-methanesulfonamidophenoxy)2-[N-(3, 4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride (KCB-328) and E-1-[(5-(4-chlorophenyl)-2-furanyl)methylene]amino-3-[4-(4-methyl-1 -piperazinyl)butyl]-2,4-imidazolidinedione dihydrochloride (azimilide), class I drugs do not aggravate adrenaline-induced arrhythmias even though some drugs prolong the QTc interval.
authors.affiliation: Department of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan. miyamoto@res.yamanashi-med.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: B
authors.initials: B
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Teramatsu
authors.forename: N N
authors.initials: NN
authors.lastname: Aye
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000037:antagonists & inhibitors*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male
chemical_list: D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D008012:Lidocaine; C042288:pilsicainide; D004206:Disopyramide; D004837:Epinephrine; C032151:cifenline