Skip to main navigation menu Skip to main content Skip to site footer

Narrative Review

Vol. 1 No. 2 (1995)

Class I and Class III Antiarrhythmic Agents: Mechanisms of Action and the Problem of Proarrhythmic Activity

  • Vidal Essebag
November 9, 2020




  1. Lucchesi BR, Chi L, Friedrichs GS, Black SC, Uprichard ACG. Antiarrhythmic versus antifibrillatory actions: inference from experimental studies. American Journal of Cardiology 72: 25F-44F; 1993.
  2. Mitchell LB. Treatment of ventricular arrhythmias after recovery from myocardial infarction. Annual Review of Medicine 45: 119-38; 1994.
  3. Stanton MS. Class I antiarrhythmic drugs: quinidine, procainamide, disopyramide, lidocaine, mexiletine, tocainamide, phenytoin, moricizine, flecainide, propafenone. In: Zipes DP, Jalife J, editors. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, PA: WB Saunders Company; 1995.
  4. Kodama I, Honjo H, Kamiya K, Toyama J. Two types of sodium channel block by class I antiarrhythmic drugs studied by using Vmax of action potential in single ventricular myocytes. Journal of Molecular and Cellular Cardiology 22(1): 1-12; 1990.
  5. Bigger JT, Hoffman BF. Antiarrhythmic drugs. In: Gilman AG, Rall TW, Nies AS, Taylor P, editors. Goodman and Gilman's the Pharmacological Basis of Therapeutics. New York, NY: McGraw Hill; 1990.
  6. Salata JJ, Wasserstorm JA. Effects of quinidine on action potentials and ionic currents in isolated canine ventricular myocytes. Circulation Research 62: 324-337; 1988.
  7. Kohlhardt M, Fichtner H, Frobe U, Herzig JW. On the mechanisms of drug-induced blockade of Na+ currents: interaction of antiarrhythmic compounds with DPI-modified single cardiac Na+ channels. Circulation Research 64: 867-881; 1989.
  8. Duan D, Fermini B, Nattel S. Potassium channel blocking properties of propafenone in rabbit atrial myocytes. Journal of Pharmacology and Experimental Therapeutics 264: 1113-1123; 1993.
  9. Cardiac Arrhythmia Suppression Trial (CAST) investigators preliminary report: effect of encainide and flecainide on mortality in a randomised trial of arrhythmia suppression after myocardial infarction. New England Journal of Medicine 321: 406-412; 1989.
  10. Campbell TJ. Subclassification of class I antiarrhythmic drugs: enhanced relevance after CAST. Cardiovascular Drugs and Therapy 6(5): 519-528; 1992.
  11. Singh BN. Controlling cardiac arrhythmias: to delay conduction or to prolong refractoriness? Cardiovascular Drugs and Therapy 3: 671-674; 1990.
  12. Wit AL, Coromilas J. Role of alterations in refractoriness and conduction in the genesis of reentrant arrhythmias: implications for antiarrhythmic effects of class III drugs. American Journal of Cardiology 72(16): 3F-12F; 1993.
  13. Hohnloser SH. Indications and limitations of class II and III antiarrhythmic drugs in atrial fibrillation. Pace-Pacing & Clinical Electrophysiology 17(5 Pt 2): 1019-1025; 1994.
  14. Wong J, Feng J, Nattel S. Class III antiarrhythmic drug action in experimental atrial fibrillation: differences in reverse use dependence and effectiveness between d-sotalol and the new antiarrhythmic drug ambasilide. Circulation 90: 2032-2040; 1994.
  15. Zanetti LA. Sotalol: a new class III antiarrhythmic agent. Clinical Pharmacy 12(12): 883-891; 1993.
  16. Hoffmeister HM, Beyer M, Seipel L. Hemodynamic effects of the D- and L-isomers of sotalol on normal myocardium. Cardiovascular Drugs and Therapy 5(6): 1027-1033; 1991.
  17. Leatham EW, Holt DW, McKenna WJ. Class III antiarrhythmics in overdose. Presenting features and management principles. Drug Safety 9(6): 450-462; 1993.
  18. Beyer T, Brachmann J, Kubler W. Comparative effects of d-sotalol and l-sotalol on the atrioventricular node of the rabbit heart. Journal of Cardiovascular Pharmacology 22(2): 240-246; 1993.
  19. Mason JW on behalf of ESVEM investigators: A comparison of seven anti-arrhythmic drugs in patients with ventricular tachyarrhythmias. New England Journal of Medicine 329: 452-458; 1993.
  20. Fitton A, Sorkin EM. Sotalol: an updated review of its pharmacological properties and therapeutic use in cardiac arrhythmias. Drugs 46(4): 678-719; 1993.
  21. Waldo AL, Camm AJ, Deruyter H, et al. Survival with oral d-sotalol in patients with left ventricular dysfunction after myocardial infarction - rationale, design, and method (The SWORD trial). American Journal of Cardiology 75(15): 1023-1027; 1995.
  22. Advani SV, Singh BN. Pharmacodynamic, pharmacokinetic and antiarrhythmic properties of d-sotalol, the dextro-isomer of sotalol. Drugs 49(5): 664-679; 1995.
  23. Sasyniuk BI, Brunet S. Proarrhythmic effects of d-sotalol in rabbit ventricle associated with differential effects on endocardial cells at slow heart rates. Circulation 90: I-146; 1994.
  24. Sasyniuk BI, Brunet S. Torsade de pointes induced by quinidine, d-sotalol and E-4031 in the isolated rabbit heart: importance of interval dependent dispersion of repolarization. PACE 18: 904; 1995.
  25. Nattel S. Comparative mechanisms of action of antiarrhythmic drugs. American Journal of Cardiology 72: 13F-17F; 1993.
  26. Kadish AH, Chen RF, Schmaltz S, Morady F. Magnitude and time course of beta-adrenergic antagonism during oral amiodarone therapy. Journal of the American College of Cardiology 16: 1240-1245; 1990.
  27. Middlekauff HR, Wiener I, Stevenson WG. Low-dose amiodarone for atrial fibrillation. American Journal of Cardiology 72(16): 75F-81F; 1993.
  28. Ceremuzynski L. Secondary prevention after myocardial infarction with class III antiarrhythmic drugs. American Journal Of Cardiology 72(16): 82F-86F; 1993.
  29. Camm AJ, Julian D, Janse G, et al. on behalf of the EMIAT investigators. The European Myocardial Infarct Trial (EMIAT). American Journal of Cardiology 72: 95F-98F; 1993.
  30. Sanguinetti MC: Modulation of potassium channels by antiarrhythmic and antihypertensive drugs. Hypertension 19: 228-236; 1992.
  31. Spinelli W, Moubarak IF, Parsons RW, Colatsky TJ. Cellular electrophysiology of WAY-123,398, a new class III antiarrhythmic agent: specificity of IK block and lack of reverse use dependence in cat ventricular myocytes. Cardiovascular Research 27(9): 1580-1591; 1993.
  32. Chadwick CC, Ezrin AM, O'Connor B, Volberg WA, Smith DI, et al. Identification of a specific radioligand for the cardiac rapidly activating delayed rectifier K+ channel. Circulation Research 72(3): 707-714; 1993.
  33. Martin CL, Chinn K. Contribution of delayed rectifier and inward rectifier to repolarization of the action potential: pharmacologic separation. Journal of Cardiovascular Pharmacology 19(5): 830-837; 1992.
  34. Jurkiewicz NK, Sanguinetti MC. Rate-dependent prolongation of cardiac action potentials by a methanesufonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circulation Research 72(1): 75-83; 1993.
  35. Kiehn J, Villena P, Beyer T, Brachmann J. Differential effects of the new class III agent dofetilide on potassium currents in guinea pig cardiomyocytes. Journal of Cardiovascular Pharmacology 24(4): 566-572; 1994.
  36. Sanguinetti MC, Jurkiewicz NK, Scott A, Siegl PKS. Isoproterenol antagonizes prolongation of refractory period by the Class III antiarrhythmic agent E-4031 in guinea pig myocytes: mechanism of action. Circulation Research 68: 77-84; 1991.
  37. Wallace AA, Stupienski RF, Brookes LM, Selnick HG, Claremon DA, Lynch JJ Jr. Cardiac electrophysiologic and inotropic actions of new and potent methanesulfonanilide class III antiarrhythmic agents in anesthetized dogs. Journal of Cardiovascular Pharmacology 18(5): 687-695; 1991.
  38. Baskin EP, Serik CM, Wallace AA, et al. Effects of new and potent methanesulfonanilide class III antiarrhythmic agents on myocardial refractoriness and contractility in isolated cardiac muscle. Journal of Cardiovascular Pharmacology 18(3): 406-414; 1991.
  39. Nabih MA, Prcevski P, Fromm BS, Lavine SJ, et al. Effect of ibutilide, a new class III agent, on sustained atrial fibrillation in a canine model of acute ischemia and myocardial dysfunction induced by microembolisation. Pace-Pacing and Clinical Electrophysiology 16(10): 1975-1983; 1993.
  40. Buchanan LV, Turcotte UM, Kabell GG, Gibson JK. Antiarrhythmic and electrophysiologic effects of ibutilide in a chronic canine model of atrial flutter. Journal of Cardiovascular Pharmacology 22(1): 10-14; 1993.
  41. Lee KS. Ibutilide, a new compound with potent class III antiarrhythmic activity, activates a slow inward Na+ current in guinea pig ventricular cells. Journal of Pharmacology and Experimental Therapeutics 262(1): 99-108; 1992.
  42. Lee KS, Tsai TD, Lee EW. Membrane activity of class III antiarrhythmic compounds; a comparison between ibutilide, d-sotalol, E-4031, sematilide and dofetilide. European Journal of Pharmacology 234(1): 43-53; 1993.
  43. Woosley RL. New antiarrhythmic drugs. In: Zipes DP, Jalife J, editors. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, PA: WB Saunders Company; 1995.
  44. Buchanan LV, Kabell G, Brunden MN, Gibson JK. Comparative assessment of ibutilide, d-sotalol, clofium, E-4031, and UK-68,798 in a rabbit model of proarrhythmia. Journal of Cardiovascular Pharmacology 22(4): 540-549; 1993.
  45. Busch AE, Malloy K, Groh WJ, Varnum MD, Adelman JP, Maylie J. The novel class III antiarrhythmics NE-10064 and NE-10133 inhibit IsK channels expressed in Xenopus oocytes and IKs in guinea pig cardiac myocytes. Biochemical and Biophysical Research Communications 202(1): 265-270; 1994.
  46. Fermini B, Jurkiewicz NK, Jow B, et al. Use-dependent effects of the class III antiarrhythmic agent NE-10064 (azimilide) on cardiac repolarization - block of delayed rectifier potassium and l-type calcium currents. Journal of Cardiovascular Pharmacology 26(2): 259-271; 1995.
  47. Bril A, Faivre JF, Forest MC, et al. Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking properties, in guinea pig cardiac isolated preparations. Journal of Pharmacology and Experimental Therapeutics 273(3): 1264-1272; 1995.
  48. Gout B, Nichols AJ, Feuerstein GZ, Bril A. Antifibrillatory effects of BRL-32872 in anesthetized Yucatan minipigs with regional myocardial ischemia. Journal of Cardiovascular Pharmacology 26(4): 636-644; 1995.
  49. Sasyniuk BI, Carmeliet E. Role of potassium channel modulators in the treatment of cardiac arrhythmias. In: Cuello AC, Collier B, editors. Pharmacological Sciences: Perspectives for Research and Therapy in the Late 1990s. Basel: Birkhauser; 1995.
  50. Hondeghem LM. Development of class III antiarrhythmic agents. Journal of Cardiovascular Pharmacology 20(Suppl. 2): S17-S22; 1992.


Metrics Loading ...