Pharmacology of the antiarrhythmic drugs

  • Penelope A. Boyden
  • Andrew L. Wit


Antiarrhythmic drugs are compounds which influence the electrical activity of the heart and may thereby alter or abolish the abnormalities in impulse initiation and conduction which cause cardiac arrhythmias. Until the early 1960s only two drugs, quinidine and procainamide, were used widely as antiarrhythmics in the United States. During the past 15 years there has been a continuous growth in the number of agents available. In this chapter we discuss the electrophysiological bases for the action of antiarrhythmic drugs and review their pharmacological properties. The discussion will include all antiarrhythmic drugs currently approved for clinical use in the United States, as well as some of the promising agents undergoing clinical trials.


Antiarrhythmic Drug Action Potential Duration Purkinje Fiber Effective Refractory Period Action Potential Amplitude 
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  1. 1.
    Moe GK, Abildskov JA: Antiarrhythmic Drugs, Inc. In: Goodman LS, Gilman A (eds) The Pharmacological Basis of Therapeutics. Macmillan Publ Co, Inc, New York, 1970, pp 709–727.Google Scholar
  2. 2.
    Frey W: Weitere Erfahrungen mit Chiniden bei absoluter Herzunregelmässigkeit. Wien Klin Wochenschr 55:849–861, 1918.Google Scholar
  3. 3.
    Hoffman BF: The action of quinidine and procainamide on single fibers of dog ventricle and specialized conducting system. An Acad Bras Cienc 29:365–368, 1958.Google Scholar
  4. 4.
    Vaughan Williams EM, Szekeres L: A comparison of tests of antifibrillatory action. Br J Pharmacol 17:424–432, 1961.Google Scholar
  5. 5.
    West TC, Amory DW: Single fiber recording of the effect of quinidine at atrial pacemaker sites in the isolated right atrium of the rabbit. J Pharmacol Exp Ther 130:183–193, 1960.PubMedGoogle Scholar
  6. 6.
    Chen CM, Gettes LS, Katzung BG: Effects of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dv/dt) max in guinea pig ventricular myocardium. Circ Res 37:20–29, 1975.PubMedGoogle Scholar
  7. 7.
    Hondeghem LM, Katzung BG: Test of a model of antiarrhythmic drug action: effects of quinidine and lidocaine on myocardial conduction. Circulation 61:1217–1224, 1980.PubMedGoogle Scholar
  8. 8.
    Johnson EA, McKinnon MG: The differential effect of quinidine and pyrilamine on the myocardial action potential at different rates of stimulaton. J Pharmacol Exp Ther 120:460–468, 1957.PubMedGoogle Scholar
  9. 9.
    Grant AO, Trantham JL, Brown KK, Strauss HC: pH-Dependent effects of quinidine on the kinetics of dv/dt max in guinea pig ventricular myocardium. Circ Res 50:210–217, 1982.PubMedGoogle Scholar
  10. 10.
    Hondeghem LM, Katzung BG: Time and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta 474:373–398, 1977.Google Scholar
  11. 11.
    Nattel S, Elharrar V, Zipes D, Bailey JC: pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers. Circ Res 48:55–61, 1981.PubMedGoogle Scholar
  12. 12.
    Dreifus LS, Azevedo IH, Watanabe Y: Electrolyte and antiarrhythmic drug action. Am Heart J 88:95–107, 1974.PubMedGoogle Scholar
  13. 13.
    Watanabe Y, Dreifus L, Likoff W: Electrophysiological antagonism and synergism of potassium and antiarrhythmic agents. Am J Cardiol 12:702–710, 1963.PubMedGoogle Scholar
  14. 14.
    Hoffman BF, Rosen MR, Wit AL: Electrophysiology and pharmacology of cardiac arrhythmias VII. Cardiac effects of quinidine and procainamide. Am Heart J 90:117–122, 1975.PubMedGoogle Scholar
  15. 15.
    Hondeghem LM: Effects of lidocaine, phenytoin and quinidine on ischemic canine myocardium. J Electrocardiol 9:203–209, 1976.PubMedGoogle Scholar
  16. 16.
    Nawrath H: Action potential, membrane currents and force of contraction in mammalian heart muscle fibers treated with quinidine. J Pharmacol Exp Ther 216:176–182, 1981.PubMedGoogle Scholar
  17. 17.
    Vaughan Williams EM: The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential electrodes. Br J Pharmacol 13:276–287, 1958.Google Scholar
  18. 18.
    Mirro MJ, Watanabe AM, Bailey JC: Electrophysiological effects of the optical isomers of disopyramide and quinidine in the dog. Dependence on stereochemistry. Circ Res 48:867–874, 1981.PubMedGoogle Scholar
  19. 19.
    Colatsky T: Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibers: an effect on steady-state sodium currents? Circ Res 50:17–27, 1982.PubMedGoogle Scholar
  20. 20.
    Mirro MJ, Manalan AS, Bailey JC, Watanabe AM: Anticholinergic effects of disopyramide and quinidine on guineapig myocardium; mediation by direct muscarinic receptor blockade. Circ Res 47:855–865, 1980.PubMedGoogle Scholar
  21. 21.
    Carmeliet E, Saikawa T: Shortening of the action potential and reduction of pacemaker activity by lidocaine, quinidine and procainamide in sheep cardiac Purkinje fibers: an effect on Na or K currents? Circ Res 50:257–272, 1982.PubMedGoogle Scholar
  22. 22.
    De Francesco D: a new interpretation of the pacemaker current in Purkinje fibers. J Physiol (Lond) 314:359–376, 1981.Google Scholar
  23. 23.
    Grant AO, Katzung BG: The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig. J Pharmacol Exp Ther 196:407–419, 1976.PubMedGoogle Scholar
  24. 24.
    Henning B, Wit AL: Multiple mechanisms of antiarrhythmic drug action on delayed afterdepolarizations in canine coronary sinus. Am J Cardiol 49:913, 1982 (abstract).Google Scholar
  25. 25.
    Henning B, Vereecke J, Carmeliet E, Wit AL: Block of transient inward current by TTX and local anesthetics. Circulation (Suppl II): II-356, 1982.Google Scholar
  26. 26.
    Josephson ME, Seides SF, Batsford WP, Weisfogel GM, Akhtar M, Carcacta AR, Lau SH, Damato AN: The electrophysiological effects of intramuscular quinidine on the atrioventricular conducting system in man. Am Heart J 87:55–64, 1974.PubMedGoogle Scholar
  27. 27.
    Roberts J, Stadter RP, Cairoli V, Modell W: Relationship between adrenergic activity and cardiac actions on quinidine. Circ Res 11:758–764, 1962.Google Scholar
  28. 28.
    Schmid PG, Nelson LD, Mark AL, Heistad DD, Abboud FM: Inhibition of adrenergic vasoconstriction by quinidine. J Pharmacol Exp Ther 188:124–134, 1974.PubMedGoogle Scholar
  29. 29.
    Mason JW, Winkle RA, Rider AK, Stinson EB, Harrison DC: The Electrophysiologic effects of quinidine in the transplanted human heart. J Clin Invest 59:481–489, 1977.PubMedGoogle Scholar
  30. 30.
    Wallace AG, Cline RE, Sealy WC, Young WG, Troyer WG: Electrophysiologic effect of quinidine: studies using chronically implanted electrodes in awake dogs with and without cardiac denervation. Circ Res 19:960–969, 1966.PubMedGoogle Scholar
  31. 31.
    Bigger JR Jr: Management of arrhythmias. In: Braunwald E (ed) Heart Disease: A Textbook of Cardiovascular Medicine. Saunders, Philadelphia, 1980, pp 691–743.Google Scholar
  32. 32.
    Heissenbuttel RH, Bigger JT Jr: The effect of oral quinidine on intraventricular conduction in man: correlation of plasma quinidine with changes in QRS duration. Am Heart J 80:453–462, 1970.PubMedGoogle Scholar
  33. 33.
    Lu G: The mechanism of the vasomotor action of quinidine. J Pharmacol Exp Ther 103:441–449, 1951.PubMedGoogle Scholar
  34. 34.
    Ferrer IM, Harvey RM, Wrko L, Dresdale DT, Cournand A, Richards DW Jr: Some effects of quinidine sulfate on the heart and circulation in man. Am Heart J 36:816–837, 1948.PubMedGoogle Scholar
  35. 35.
    Markiewicz W, Winkle RA, Binetti G, Kernoff R, Harrison DC: Normal myocardial contractile state in the presence of quinidine. Circulation 53:101–106, 1976.PubMedGoogle Scholar
  36. 36.
    Parmley WW, Braunwald E: Comparative myocardial depressant and antiarrhythmic properties of d-propranolol, dl propranolol and quinidine. J Pharmacol Exp Ther 158:11–21, 1967.PubMedGoogle Scholar
  37. 37.
    Greenblatt DJ, Pfeifer HJ, Ochs HR, Franke K, Mac-Laughlin DS, Smith TW, Koch-Weser J: Pharmacokinetics of quinidine in humans after intravenous, intramuscular, and oral administration. J Pharmacol Exp Ther 202: 365–378, 1977.PubMedGoogle Scholar
  38. 38.
    Belief S: The Clinical Disorders of the Heart Beat. Lea and Febiger, Philadelphia, 1971.Google Scholar
  39. 39.
    Conn HL Jr, Luchi RJ: Some quantitative aspects of the binding of quinidine compounds by human serum albumin. J Clin Invest 40:509–516, 1961.PubMedGoogle Scholar
  40. 40.
    Scherlis L, Gonzales LF, Bessman SP: Quinidine: arterial, venous, coronary sinus and myocardial concentrations. J Clin Invest 40:60–66, 1961.PubMedGoogle Scholar
  41. 41.
    Ueda CT, Hirschfeld DS, Scheinman MM: Disposition kinetics of quinidine. Clin Pharmacol Ther 19:30–36, 1976.PubMedGoogle Scholar
  42. 42.
    Ueda CT, Williamson BJ, Bzindzio BS: Absolute quinidine bioavailability. Clin Pharmcol Ther 20:260–265, 1976.Google Scholar
  43. 43.
    Palmer KH, Martin B, Baggett B, Wall ME: The metabolic fate of orally administered quinidine gluconate in humans. Biochem Pharmacol 18:1845–1860, 1969.Google Scholar
  44. 44.
    Nwangwu PU, Holcslaw TL, Small TD, Stohs SJ: A preliminary evaluation of 6’-hydroxycinchonine as an antiarrhythmic agent. Pharmacologist 19:152, 1977 (abstract).Google Scholar
  45. 45.
    Drayer DE, Lowventhal DT, Restivo KM, Schwartz A, Cook CE, Reidenberg MM: Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. Clin Pharmacol Ther 24:31–39, 1978.PubMedGoogle Scholar
  46. 46.
    Gerhardt RD, Knouss RF, Thyrum PT, Luchi RJ, Morris JT: Quinidine excretion in aciduria and alkaluria. Ann Intern Med 71:927–933, 1969.PubMedGoogle Scholar
  47. 47.
    Arnsdorf MF, Hsieh Y: Antiarrhythmic agents. In: Hurst JW (ed) The Heart. McGraw Hill Inc, New York, 1978, pp 1943–1963.Google Scholar
  48. 48.
    Conrad KA, Molk BL, Chidsey CA: Pharmacokinetic studies of quinidine in patients with arrhythmias. Circulation 55:1–7, 1977.PubMedGoogle Scholar
  49. 49.
    Leahey EB Jr, Reiffel JA, Drusin RE, Heissenbuttel RH, Lovejoy WP, Bigger JT Jr: Interaction between quinidine and digoxin. J Am Med Assoc 240:533–534, 1978.Google Scholar
  50. 50.
    Bigger JT Jr: The quinidine-digoxin interaction. Mod Concepts Cardiovasc Dis 51:73–78, 1982.PubMedGoogle Scholar
  51. 51.
    Doherty JE, Straub KD, Murphey ML, de Soyza N, Bissett JK, Kane JJ: Digoxin-quinidine interaction changes in canine tissue concentration from steady state with quinidine. Am J Cardiol 45:1196–1200, 1980.PubMedGoogle Scholar
  52. 52.
    Data JL, Wilkinson GR, Nies AS: Interaction of quinidine with anticonvulsant drugs. N Engl J Med 294:699–702, 1976.PubMedGoogle Scholar
  53. 53.
    Koch-Weser J: Quinidine-induced hypoprothrombinemic hemorrhage in patients on chronic warfarin therapy. Ann Intern Med 68:511–577, 1968.PubMedGoogle Scholar
  54. 54.
    Shep DS, Myerberg R: Drug interactions involving antiarrhythmic drugs. In: Petrie JC(ed) Cardiovascular and Respiratory Disease Therapy. Elsevier, Amsterdam, 1980, pp 43–59.Google Scholar
  55. 55.
    Mautz FR: The reduction of cardiac irritability by the epicardial and systemic administration of drugs as a protection in cardiac surgery. J Thorac Surg 5:612–618, 1936.Google Scholar
  56. 56.
    Mark LC, Kayden HJ, Steele JM, Cooper JR, Berlin I, Rovenstein EA, Brodie BB: The physiological disposition and cardiac effects of procaine amide. J Pharmacol Exp Ther 102:5–15, 1951.PubMedGoogle Scholar
  57. 57.
    Rosen MR, Gelband H, Hoffman BF: Canine electrocardiographic and cardiac electrophysiologic changes induced by procainamide. Circulation 46:528–536, 1972.PubMedGoogle Scholar
  58. 58.
    Rosen M, Gelband H, Merker C, Hoffman B: Effects of procaine amide on the electrophysiological properties of the canine ventricular conducting system. J Pharmacol Exp Ther 185:438–446, 1973.PubMedGoogle Scholar
  59. 59.
    Sada H, Kojima M, Ban T: Effect of procainamide on transmembrane action potential in guinea pig papillary muscle as affected by external potassium concentration. Naunyn Schmiedebergs Arch Pharmacol 309:179–190, 1979.PubMedGoogle Scholar
  60. 60.
    Arnsdorf MF, Bigger JT: The effect of procaineamide on components of excitability in long mammalian cardiac Purkinje fibers. Circ Res 38:115–122, 1976.PubMedGoogle Scholar
  61. 61.
    Hordof A, Edie R, Malm J, Rosen M: Effects of procaineamide and verapamil on electrophysiologic properties of human atrial tissues. Pediatr Res 9:267, 1975 (abstract).Google Scholar
  62. 62.
    Arnsdorf MF: The effect of antiarrhythmic drugs on triggered sustained rhythmic activity in cardiac Purkinje fibers. J Pharmacol Exp Ther 201:689–700, 1977.PubMedGoogle Scholar
  63. 63.
    Schmid PG, Nelson LD, Heistad DD, Mark AL, Abboud FM: Vascular effects of procaineamide in the dog. Predominance of the inhibitory effect on ganglionic transmission. Circ Res 35:948–960, 1974.PubMedGoogle Scholar
  64. 64.
    Wyse DG, McAnulty JH, Stadius M, Rahimtoola SH: Electrophysiologic effects of procainamide in patients with normal and prolonged sinoatrial conduction times. Am J Cardiol 41:386, 1978 (abstract).Google Scholar
  65. 65.
    Scheinman MM, Weiss AN, Shafton E, Benowitz N, Rowland M: Electrophysiologic effects of procaine amide on patients with intraventricular conduction delay. Circulation 49:522–529, 1974.PubMedGoogle Scholar
  66. 66.
    Josephson ME, Carcacta AR, Riccuiti MA, Lau SH, Damato AN: Electrophysiologic properties of procainamide in man. Am J Cardiol 33:596–603, 1974.PubMedGoogle Scholar
  67. 67.
    Giardina EGV, Heissenbuttel RH, Bigger JT Jr: Intermittent intravenous procaineamide to treat ventricular arrhythmias. Correlation of plasma concentration with effect on arrhythmias, electrocardiogram and blood pressure. Ann Intern Med 78:183–193, 1973.PubMedGoogle Scholar
  68. 68.
    Giardina EGV, Bigger JT Jr: Procaine amide against reentrant ventricular arrhythmias: lengthening R-V intervals of coupled ventricular premature depolarizations as an insight into the mechanism of action of procaine amide. Circulation 48:959–970, 1973.PubMedGoogle Scholar
  69. 69.
    Bigger JT Jr, Giardina EGV: The pharmacology and clinical uses of lidocaine and procainamide. M Coll Va Q 9:65–71, 1973.Google Scholar
  70. 70.
    Bigger JT Jr, Heissenbuttel RH: The use of procaine amide and lidocaine in the treatment of cardiac arrhythmias. Prog Cardiovasc Dis 11:515–534, 1969.PubMedGoogle Scholar
  71. 71.
    Giardina EGV, Dreyfuss J, Bigger JR Jr, Shaw JM, Schreiber EC: Metabolism of procainamide in normal and cardiac subjects. Clin Pharmacol Ther 19:339–351, 1976.PubMedGoogle Scholar
  72. 72.
    Koch-Weser J, Klein SW: Procainamide dosage schedules, plasma concentrations and clinical effects. J Am Med Assoc 215:1454–1456, 1971.Google Scholar
  73. 73.
    Hoffman BF, Rosen MR, Wit AL: Electrophysiology and pharmacology of cardiac arrhythmias VII. Cardiac effects of quinidine and procaine amide A. Am Heart J 89: 804–808, 1975.PubMedGoogle Scholar
  74. 74.
    Koch-Weser J, Klein SW, Foo-Canto LL, Kastor JA, De-Sanctis RW: Antiarrhythmic prophylaxis with procainamide in acute myocardial infarction. N Engl J Med 281: 1253–1260, 1969.PubMedGoogle Scholar
  75. 75.
    Dreyfuss J, Bigger JT Jr, Cohen AL, Schreiber EC: Metabolism of procainamide in rhesus monkey and man. Clin Pharmacol Ther 13:336–371, 1972.Google Scholar
  76. 76.
    Dangman KH, Hoffman BF: In vivo and in vitro antiarrhythmic and arrhythmogenic effects of N-acetylprocainamide. J Pharmacol Exp Ther 217:851–862, 1981.PubMedGoogle Scholar
  77. 77.
    Elison J, Strong JM, Lee WK, Atkinson AJ Jr: Antiarrhythmic potency of N-acetylprocainamide. Clin Pharmacol Ther 17:134–140, 1975.Google Scholar
  78. 78.
    Giardina EGV, Stein RM, Bigger JT Jr: The relationship between metabolism of procainamide and sulfamethazine. Circulation 55:388–394, 1977.Google Scholar
  79. 79.
    Galeazzi RL, Sheiner LB, Lock T, Benet LS: The renal elimination of procainamide. Clin Pharmacol Ther 19: 55–62, 1976.PubMedGoogle Scholar
  80. 80.
    Gibson TP, Lowenthal DT, Nelson HA, Briggs WA: Elimination of procainamide in end stage renal failure. Clin Pharmacol Ther 17:321–329, 1975.PubMedGoogle Scholar
  81. 81.
    Ladd AT: Procainamide-induced lupus erythematosus. N Engl J Med 267:1357–1358, 1962.PubMedGoogle Scholar
  82. 82.
    Davies DM, Beedie MA, Rawlins MD: Antinuclear antibodies during procainamide treatment and drug acetylation. Br Med J 3:682–684, 1975.PubMedGoogle Scholar
  83. 83.
    Mokler CM, Van Arman CG: Pharmacology of a new antiarrhythmic agent α-disopropylamino α-phenyl-α-(2-pyridyl)-butyramide (SC-7031). J Pharmacol Exp Ther 136:114–124, 1962.PubMedGoogle Scholar
  84. 84.
    Mirro MJ, Watanabe AM, Bailey JC: Electrophysiological effects of disopyramide and quinidine on guinea pig atriaand canine cardiac Purkinje fibers. Circ Res 46:660–668, 1980.PubMedGoogle Scholar
  85. 85.
    Sekija A, Vaughan Williams EM: A comparison of the anti-fibrillatory actions and effects on intracellular cardiac potentials of pronetholol, disopyramide, quinidine. Br J Pharmacol 21:473–487, 1963.Google Scholar
  86. 86.
    Kus T, Sasyniuk BI: Electrophysiological actions of disopyramide phosphate on canine ventricular muscle and Purkinje fibers. Circ Res 37:844–854, 1975.PubMedGoogle Scholar
  87. 87.
    Danilo P Jr, Hordof AJ, Rosen MR: Effect of disopyramide on electrophysiologic properties of canine cardiac Purkinje fibers. J Pharmacol Exp Ther 201:701–710, 1977.PubMedGoogle Scholar
  88. 88.
    Kus T, Sasyniuk BI: The electrophysiological effects of disopyramide phosphate on canine ventricular muscle and Purkinje fibers in normal and low potassium. Can J Physiol Pharmacol 56:139–149, 1978.PubMedGoogle Scholar
  89. 89.
    Sasyniuk BI, Kus T: Effects of disopyramide phosphate (DP) on membrane responsiveness, conduction and refractoriness in infarcted canine ventricle. Fed Proc 35:235, 1976.Google Scholar
  90. 90.
    Chiba S, Kobayashi M, Furukawa Y: Effects of disopyramide on SA nodal pacemaker activity and contractility in the isolated blood perfused atrium of the dog. Eur J Pharmacol 57:13–19, 1979.PubMedGoogle Scholar
  91. 91.
    Seipel L, Breithardt G: Sinus recovery time after disopyramide phosphate. Am J Cardiol 37:1118–1119, 1976.PubMedGoogle Scholar
  92. 92.
    LaBarre A, Strauss HC, Scheinman MM, Evans GT, Bashore T, Tiedeman JS, Wallace AG: Electrophysiologic effects of disopyramide phosphate on sinus node function in patients with sinus node dysfunction. Circulation 59: 226–235, 1979.PubMedGoogle Scholar
  93. 93.
    Befeler B, Castellanos A, Wells DE, Vagueiro MC, Yeh BK: Electrophysiologic effects of the antiarrhythmic agent disopyramide phosphate. Am J Cardiol 35:282–287, 1975.PubMedGoogle Scholar
  94. 94.
    Josephson ME, Carcacta AR, Lau SH, Gallagher JJ, Damato AN: Electrophysiological evaluation of disopyramide in man. Am Heart J 86:771–780, 1973.PubMedGoogle Scholar
  95. 95.
    Birkhead JS, Vaughan Williams EM: Dual effect of disopyramide on atrial and atrioventricular conduction and refractory periods. Br Heart J 39:657–660, 1977.PubMedGoogle Scholar
  96. 96.
    Swiryn S, Bauerfeind RA, Wyndham CRC, Dhingra RC, Palileo E, Strasberg B, Rosen KM: Effects of oral disopyramide phosphate on induction of paroxysmal supraventricular tachycardia. Circulation 64:169–175, 1981.PubMedGoogle Scholar
  97. 97.
    Kus T, Sasyniuk B: Disopyramide phosphate: it is just another quinidine? Can J Physiol Pharmacol 56:326–331, 1978.PubMedGoogle Scholar
  98. 98.
    Mathur PP: Cardiovascular effects of a newer antiarrhythmic agent - disopyramide phosphate. Am Heart J 84:764–770, 1972.PubMedGoogle Scholar
  99. 99.
    Marrott PK, Ruttley MST, Winterbottam JT, Muir JR: A study of the acute electrophysiologic and cardiovascular action of disopyramide in man. Eur J Cardiol 4:303–310, 1976.PubMedGoogle Scholar
  100. 100.
    Podrid PJ, Schoeneberger A, Lown B: Congestive heart failure caused by oral disopyramide. N Engl J Med 302:614, 1980.PubMedGoogle Scholar
  101. 101.
    Lawrie TDV: Comparison of newer anti-arrhythmic agents. Am Heart J 100(pt 2):990–994, 1980.PubMedGoogle Scholar
  102. 102.
    Kotter V, Linderer T, Schroder R: Effects of disopyramide on systemic and coronary hemodynamics and myocardial metabolism in patients with coronary artery disease: comparison with lidocaine. Am J Cardiol 46: 469–475, 1980.PubMedGoogle Scholar
  103. 103.
    Walsh RA, Horwitz LD: Adverse hemodynamic effects of intravenous disopyramide compared with quinidine in conscious dogs. Circulation 60:1053–1058, 1979.PubMedGoogle Scholar
  104. 104.
    Vismara L: Clinical studies of norpace (II). Angiology 26:132–136, 1975.PubMedGoogle Scholar
  105. 105.
    Chien YW, Lambert HJ, Karim A: Comparative binding of disopyramide phosphate and quinidine sulfate to human plasma proteins. J Pharmacol Sci 63:1877–1879, 1974.Google Scholar
  106. 106.
    Hinderling PH, Bres J, Garrett ER: Protein binding and erythrocyte partitioning of disopyramide and its monodealkylated metabolite. J Pharmacol Sci 63:1684–1690, 1974.Google Scholar
  107. 107.
    Harrison DC, Meffin PJ, Winkle RA: Clinical Pharmacokinetics of antiarrhythmic drugs. Prog Cardiovasc Dis 20: 217–242, 1977.PubMedGoogle Scholar
  108. 108.
    Hinderling PH, Garrett ER: Pharmacodynamics of the antiarrhythmic disopyramide in healthy humans: Correlation of the kinetics of the drug and its effects. J Pharmacokinet Biopharm 4:231–242, 1976.PubMedGoogle Scholar
  109. 109.
    Karim A: The pharmacokinetics of Norpace. Angiology 26:85–98, 1975.PubMedGoogle Scholar
  110. 110.
    Baines MW, Davies JE, Kellet DN, Munt PL: Some pharmacological effects of disopyramide and a metabolite. J Int Med Res 4:5–7, 1976.PubMedGoogle Scholar
  111. 111.
    Grant AM, Marshall RJ, Ankier SI: Some effects of disopyramide and its N-dealkylated metabolite on isolated nerve and cardiac muscle. Eur J Pharmacol 49:389–394, 1978.PubMedGoogle Scholar
  112. 112.
    Aitio ML, Aitio A: Induction of disopyramide N-dealkylation by phenobarbital and disopyramide in rat liver. Arch Intern Pharmacodyn Ther 239:16–23, 1979.Google Scholar
  113. 113.
    Hinderling PH, Garrett ER: Pharmacokinetics of the antiarrhythmic disopyramide in healthy humans. J Pharmacokinet Biopharm 4:119–229, 1976.Google Scholar
  114. 114.
    Whiting B, Elliot HL: Disopyramide in renal impairment. Lancet 2:1363, 1977.PubMedGoogle Scholar
  115. 115.
    Rangno RE, Wanuch W, Ogilvie RI: Correlation of disopyramide pharmacokinetics with efficacy in ventricular tachyarrhythmias. J Int Med Res 4(Supp l):54–58, 1976.PubMedGoogle Scholar
  116. 116.
    Ilett K, Madsen BW, Woods JD: Disopyramide kinetics in patients with acute myocardial infarction. Clin Pharmacol Ther 26:1–7, 1979.PubMedGoogle Scholar
  117. 117.
    Ward J W, Kinghom CR: The pharmacokinetics of disopyramide following myocardial infarction with special reference to oral and intravenous dose regimens. J Int Med Res 4(Supp 1):49–53, 1976.PubMedGoogle Scholar
  118. 118.
    Lofgren N: Studies on local anesthetics. Xylocaine, A New Synthetic Drug. Ivar Haeggstroms, Stockholm, 1948 (reprinted by Marin Press, Inc, Worcester, MA).Google Scholar
  119. 119.
    Southworth JL, McKusick V A, Pierce EC, Rawson FL Jr: Ventricular fibrillation precipitated by cardiac catheterization. J Am Med Assoc 143:717–720, 1950.PubMedGoogle Scholar
  120. 120.
    Davis LD, Temte JV: Electrophysiological actions of lidocaine on canine ventricular muscle and Purkinje fibers. Circ Res 24:639–655, 1969.PubMedGoogle Scholar
  121. 121.
    Bigger JT Jr, Mandel WT: Effect of lidocaine on transmembrane potentials of ventricular muscle and Purkinje fibers. J Clin Invest 49:63–77, 1970.PubMedGoogle Scholar
  122. 122.
    Mandel WJ, Bigger JT Jr: Electrophysiologic effects of lidocaine on isolated canine and rabbit atrial tissues. J Pharmacol Exp Ther 178:81–93, 1971.PubMedGoogle Scholar
  123. 123.
    Weld FM, Bigger JT Jr: Effect of lidocaine on the early inward transient current in sheep cardiac Purkinje fibers. Circ Res 37:630–639, 1975.PubMedGoogle Scholar
  124. 124.
    Bean BP, Cohen CJ, Tsien RW: Lidocaine Binding to Resting and Inactivated cardiac sodium channels. Biophys J 33:208, 1981.Google Scholar
  125. 125.
    Lee KS, Hume JR, Giles W, Brown AM: Sodium current depression by lidocaine and quinidine in isolated ventricular cells. Nature 291:325–327, 1981.PubMedGoogle Scholar
  126. 126.
    Singh BN, Vaughan Williams EM: Effect of altering potassium concentrations on the action of lidocaine and diphenylhydantoin on rabbit atrial and ventricular muscle. Circ Res 29:286–295, 1971.PubMedGoogle Scholar
  127. 127.
    Obayashi K, Hayakawa H, Mandel WJ: Interrelationships between external potassium concentration and lidocaine: effects on the canine Purkinje fibers. Am Heart J 89:221–226, 1975.PubMedGoogle Scholar
  128. 128.
    Rosen MR, Merker C, Pippenger CE: The effects of lidocaine on the canine ECG and electrophysiologic properties of Purkinje fibers. Am Heart J 91:191–202, 1976.PubMedGoogle Scholar
  129. 129.
    Rosen MR, Hoffman BF, Wit AL: Electrophysiology and pharmacology of cardiac arrhythmias. V. Cardiac antiarrhythmic effects of lidocaine. Am Heart J 89:526–536, 1975.PubMedGoogle Scholar
  130. 130.
    Tritthart H, Fleckenstein B, Fleckenstein A: Some fundamental actions of anti-arrhythmic drugs on the excitability and contractility of single myocardial fibers. Naunyn Schmiedebergs Arch Pharmacol 269:212–219, 1971.PubMedGoogle Scholar
  131. 131.
    Gintant GA, Hoffman BF: Different local anesthetic characteristics of charged and uncharged forms of lidocaine and other antiarrhythmic drugs in canine cardiac Purkinje fibers. Am J Cardiol 49:1044, 1982.Google Scholar
  132. 132.
    Gintant G, Hoffman BF, Naylor RE: The influence of molecular form on the interactions of local anesthetic-type antiarrhythmic agents with canine cardiac Na+ channel. Circ Res (in press).Google Scholar
  133. 133.
    Brennan FJ, Cranefield PF, Wit AL: Effects of lidocaine on slow response and depressed fast response action potentials of canine cardiac Purkinje fibers. J Pharmacol Exp Ther 204:312–324, 1978.PubMedGoogle Scholar
  134. 134.
    Grant AO, Strauss LJ, Wallace AG, Strauss HC: The influence of pH on the electrophysiological effects of lidocaine in guinea pig ventricular myocardium. Circ Res 47:542–550, 1980.PubMedGoogle Scholar
  135. 135.
    Lazzara R, Hope RR, El-Sherif N, Scherlag BJ: Effects of lidocaine on hypoxia and ischemic cardiac cells. Am J Cardiol 41:872–879, 1978.PubMedGoogle Scholar
  136. 136.
    Josephson I, Sperelakis N: Local anesthetic blockade of Ca+2 mediated action potentials in cardiac muscle. Eur J Pharmacol 40:201–208, 1976.PubMedGoogle Scholar
  137. 137.
    Wittig J, Harrison LA, Wallace AG: Electrophysiological effects of lidocaine on distal Purkinje fibers of the canine heart. Am Heart J 86:69–75, 1973.PubMedGoogle Scholar
  138. 138.
    Gettes LS, Reuter H: Slow recovery from inactivation of inward currents in mammalian myocardial fibers. J Physiol (Lond) 240:703–724, 1974.Google Scholar
  139. 139.
    Katzung BG: Drug effects on ventricular automaticity. Proc West Pharmacol Soc 17:15–18, 1974.Google Scholar
  140. 140.
    Imanishi S, McAllister RG Jr, Surawicz B: The effects of verapamil and lidocaine on the automatic depolarizations in guinea-pig ventricular myocardium. J Pharmacol Exp Ther 207:294–303, 1978.PubMedGoogle Scholar
  141. 141.
    Arita M, Nagamoto Y, Saikawa T: Automaticity and time dependent conducton disturbance produced in canine ventricular myocardium. Jpn Circ J 40:1408–1418, 1976.Google Scholar
  142. 142.
    Gadsby DC, Cranefield PF: Two levels of resting potential in cardiac Purkinje fibers. J Gen Physiol 70:725–746, 1977.PubMedGoogle Scholar
  143. 143.
    Mary-Rabine L, Hordof AJ, Danilo P Jr, Malm J, Rosen MR: Mechanisms for impulse initiation in isolated human atrial fibers. Circ Res 47:267–277, 1980.PubMedGoogle Scholar
  144. 144.
    Rosen MR, Danilo P: Effects of tetrodotoxin, lidocaine, verapamil and AHR-2666 on ouabain-induced delayed afterdepolarizations in canine Purkinje fibers. Circ Res 46: 117–124, 1980PubMedGoogle Scholar
  145. 145.
    Cheng TO, Wadhwa N: Sinus standstill following intravenous lidocaine administration. J Am Med Assoc 223: 790–792, 1973.Google Scholar
  146. 146.
    Lippestad CT, Forgang K: Production of sinus arrest by lignocaine. Br Med J 1:537, 1971.PubMedGoogle Scholar
  147. 147.
    Jersaty R, Kahn A, Landry A: Sinoatrial arrest due to lidocaine in a patient receiving quinidine. Chest 61:683–684, 1972.Google Scholar
  148. 148.
    Agrawal BU, Singh RB, Vaish SK: Cardiac asystole due to lidocaine in patients with digitalis toxicity. Acta Cardiol 29:341–347, 1974.PubMedGoogle Scholar
  149. 149.
    Barrett PA, Laks MM, Mandel WJ, Yamaguchi I: The electrophysiologic effects of intravenous lidocaine in the WPW syndrome. Am Heart J 100:23–33, 1980.PubMedGoogle Scholar
  150. 150.
    Rosen KM, Lau SH, Weiss MB, Damato AN: The effect of lidocaine on atrioventricular and intraventricular conduction in man. Am J Cardiol 25:1–5, 1970.PubMedGoogle Scholar
  151. 151.
    Josephson ME, Carcacta AR, Lau SH, Gallagher JJ: Effects of lidocaine on refractory periods in man. Am Heart J 84:778–786, 1972.PubMedGoogle Scholar
  152. 152.
    Allen JD, Brennan FJ, Wit AL: Actions of lidocaine on transmembrane potentials of subendocardial Purkinje fibers surviving in infarcted canine heart. Circ Res 43:470–481, 1978.PubMedGoogle Scholar
  153. 153.
    Wang CM, James CA, Maxwell RA: Effects of lidocaine on the electrophysiological properties of subendocardial Purkinje fibers surviving acute myocardial infarction. J Mol Cell Cardiol 11:669–681, 1979.PubMedGoogle Scholar
  154. 154.
    Frieden J: Antiarrhythmic drugs. VI. Lidocaine as an anti-arrhythmic agent. Am Heart J 70:713–715, 1965.PubMedGoogle Scholar
  155. 155.
    Kupersmith J, Antman EM, Hoffman BF: In vivo electro-physiologic effects of lidocaine in canine acute myocardial infarction. Circ Res 36:84–91, 1975.PubMedGoogle Scholar
  156. 156.
    El-Sherif N, Scherlag BJ, Lazzara R, Hope RR: Reentrant ventricular arrhythmias in the late myocardial infarction period. IV. Mechanism of action of lidocaine. Circulation 56:395–402, 1977.PubMedGoogle Scholar
  157. 157.
    Gerstenbluth G, Spear JF, Moore EN: Quantitative study of the effect of lidocaine on the threshold for ventricular fibrillation in the dog. Am J Cardiol 30:242–247, 1972.Google Scholar
  158. 158.
    Grossman JI, Cooper JA, Frieden J: Cardiovascular effects of infusion of lidocaine in patients with heart disease. Am J Cardiol 24:191–197, 1969.PubMedGoogle Scholar
  159. 159.
    Harrison DC, Sprouse JH, Morrow AG: The antiarrhythmic properties of lidocaine and procainamide. Circulation 29:486–491, 1963.Google Scholar
  160. 160.
    Bigger JT Jr, Hoffman BF: Antiarrhythmic Drugs. In: Gilman AG, Goodman L, Gilman A (eds) The Pharmacological Basis of Therapeutics. Macmillan, New York, 1980.Google Scholar
  161. 161.
    Benowitz NL, Forsyth RP, Melmon LK, Rowland M: Lidocaine disposition kinetics in monkey and man. Clin Pharmacol Ther 16:87–98, 1974.PubMedGoogle Scholar
  162. 162.
    Boyes RN, Scott DB, Jebson PJ, Godman MJ, Julian DG: Pharmcokinetics of lidocaine in man. Clin Pharmacol Ther 12:105–116, 1971.PubMedGoogle Scholar
  163. 163.
    Rowland M, Thomson PD, Guichard A, Melmon K: Disposition kinetics of lidocaine in normal subjects. Ann NY Acad Sci 179:383–397, 1971.PubMedGoogle Scholar
  164. 164.
    Stenson RE, Constantino RT, Harrison DC: Interrelationship of hepatic blood flow, cardiac output and blood levels of lignocaine in man. Circulation 43:205–211, 1971.PubMedGoogle Scholar
  165. 165.
    Sung CV, Truant AP: The physiological disposition of lidocaine - its comparison is some respects with procaine. J Pharmacol Exp Ther 112:432–443, 1954.PubMedGoogle Scholar
  166. 166.
    Beckett AH, Boyes RN, Appleton PJ: The metabolism and excretion of lignocaine in man. J Pharm Pharmacol 18 (Suppl):76–81, 1966.Google Scholar
  167. 167.
    Hollunger G: On the metabolism of lidocaine. II. Biotransformation of lidocaine, hydrolysis of the amide linkage. Acta Pharmacol 17:365–373, 1960.Google Scholar
  168. 168.
    Smith ER, Duce BR: The acute antiarrhythmic and toxic effects in mice and dogs of 2-ethylamino-2’6’-acetoxylidine (L-86), a metabolite of lidocaine. J Pharmacol Exp Ther 179:580–585, 1971.PubMedGoogle Scholar
  169. 169.
    Blumer J, Strong JM, Atkinson AJ: The convulsant potency of lidocaine and its N-dealkylated metabolites. J Pharmacol Exp Ther 186:31–36, 1973.PubMedGoogle Scholar
  170. 170.
    Nation RL, Triggs EJ, Selig M: Lignocaine kinetics in cardiac patients and aged subjects. Br J Clin Pharmacol 4:439–448, 1977.PubMedGoogle Scholar
  171. 171.
    Perucca E, Richens A: Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients. Br J Clin Pharmacol 8:21–31, 1979.PubMedGoogle Scholar
  172. 172.
    Nies AS, Shand DG, Wilkinson GR: Altered hepatic blood flow and drug disposition. Clin Pharmacokinet 1:135–155, 1976.PubMedGoogle Scholar
  173. 173.
    Thomson PD, Rowland M, Melmon KL: The influence of heart failure, liver disease and renal failure on disposition of lidocaine in man. Am Heart J 82:417–421, 1971.PubMedGoogle Scholar
  174. 174.
    Thomson PD, Melmon KL, Richardson JA, Cohn K, Steinbrunn W, Cudihee R, Rowland M: Lidocaine pharmcokinetics in advanced heart failure, liver disease and renal failure in humans. Ann Intern Med 78:499–508, 1973.PubMedGoogle Scholar
  175. 175.
    Prescott LF, Adjepon-Yamoah KK, Talbot RG: Impaired lignocaine metabolism in patients with myocardial infarction and cardiac failure. Br Med J 1:939–941, 1976.PubMedGoogle Scholar
  176. 176.
    Branch RA, Shand DG, Wilkinson GR, Nies AS: The reduction of lidocaine clearance by dl-propranolol: an example of a hemodynamic drug interaction. J Pharmacol Exp Ther 184:515–519, 1973.PubMedGoogle Scholar
  177. 177.
    Collinsworth KA, Strong JM, Atkinson AJ, Winkle RA, Perlroth F, Harrison DC: Pharmacokinetics and metabolism of lidocaine in patients with renal failure. Clin Pharmacol Ther 18:59–64, 1975.PubMedGoogle Scholar
  178. 178.
    Wiklund L: Human hepatic blood flow and its relation to systemic circulation during intravenous infusion of lignocaine. Acta Anaesthesiol Scand 21:148–160, 1977.PubMedGoogle Scholar
  179. 179.
    Le Lorier J, Latour Y, Grenon D, Caille G, Brosseau A, Solignac A, Du Mont G: The pharmcokinetics of lignocaine after prolonged intravenous infusions in man. Clin Res 28:624A, 1975.Google Scholar
  180. 180.
    Pfeifer HJ, Greenblatt DH, Koch-Weser J: Clinical use and toxicity of intravenous lidocaine. Am Heart J 92:168–173, 1976.PubMedGoogle Scholar
  181. 181.
    Bigger JT Jr, Heisenbuttel RH: The use of procainamide and lidocaine in the treatment of cardiac arrhythmias. In: Friedberg CK (ed) Current Status of Drug in Cardiovascular Disease. Grune and Stratton, New York, 1969, pp 125–144.Google Scholar
  182. 182.
    Investigators Brochure for Tocainide HCL. Astra Pharmaceutial Products, Inc, Jan, 1977.Google Scholar
  183. 183.
    Moore EM, Spear JF, Horowitz LN, Feldman HS, Moller RA: Electrophysiologic properties of a new anti-arrhythmic drug-tocainide. Am J Cardiol 41:703–709, 1978.PubMedGoogle Scholar
  184. 184.
    Oshita S, Sada H, Kojima M, Ban T: Effects of tocainide and lidocaine on the transmembrane action potentials as related to external potassium and calcium concentrations in guinea pig papillary muscles. Naunyn Schmeidebergs Arch Pharmacol 314:62–82, 1980.Google Scholar
  185. 185.
    Anderson JF, Mason JW, Winkle RA, Meffin PJ, Fowler RE, Peters F, Harrison DC: Clinical electrophysiologic effects of tocainide. Circulation 57:685–691, 1978.PubMedGoogle Scholar
  186. 186.
    McDevitt DG, Nies AS, Wilkinson GR, Smith RF, Woosley RL, Oates JA: Antiarrhythmic effects of a lidocaine congener, tocainide, 2-amino-2’, 6’-propionoxylidine, in man. Clin Pharmacol Ther 19:396–402, 1976.PubMedGoogle Scholar
  187. 187.
    Coltart DJ, Berndt TB, Kernoff R, Harrison DC: Antiarrhythmic and circulatory effects of astra W36075, A new lidocaine like agent. Am J Cardiol 34:35–41, 1974.PubMedGoogle Scholar
  188. 188.
    Nyquist O, Forssell G, Nordlander R, Schenck-Gustafsson K: Hemodynamic and antiarrhythmic effects of tocainide in patients with acute myocardial infarction. Am Heart J 100(pt 2): 1000–1005, 1980.PubMedGoogle Scholar
  189. 189.
    Winkle RA, Anderson JL, Peters F, Meffin PJ, Fowler RE, Harrison DC: The hemodynamic effects of intravenous tocainide in patients with heart disease. Circulation 57:787–792, 1978.PubMedGoogle Scholar
  190. 190.
    Lalka D, Meyer MB, Duce BR: Kinetics of oral antiarrhythmic lidocaine congener tocainide. Clin Pharmacol Ther 19:757–776, 1976.PubMedGoogle Scholar
  191. 191.
    Winkle RA, Mason JW, Harrison DC: Tocainide of drug-resistent ventricular arrhythmias: efficacy, side effects and lidocaine responsiveness for predicting tocainide success. Am Heart J 100(pt 2): 1031–1036, 1980.PubMedGoogle Scholar
  192. 192.
    Elvin AT, Keenagham JB, Byrnes EW, Tenthorey PA, McMaster PD, Takman BH, Lalka D, Manon CV, Baer T, Wolshin EM, Meyer MB: Conjugation of tocainide in man: evidence for a novel pathway of biotransformation for a primary amine. Pharmacologist 18:114, 1976 (abstract).Google Scholar
  193. 193.
    Elvin AT, Keenaghan JB, Byrnes EQ, Tenthorey PA, McMaster PD, Takman BH, Lalka D, Manon CV, Baer DT, Wolshin EM, Meyer MB, Ronfeld RA: Tocainideconjugation in humans: novel biotransformation pathway for a primary amine. J Pharmacol Sci 69:47–49, 1980.Google Scholar
  194. 194.
    Venkataramanan R, Axelson JE: Dose-dependent pharmcokinetics of tocainide in the rat. J Pharmacol Exp Ther 215:231–234, 1980.PubMedGoogle Scholar
  195. 195.
    Graffner C, Couradson T-B, Hofrendahl S, Ryden L: Tocainide kinetics after intravenous and oral administration in healthy subjects and in patients with acute myocardial infarction. Clin Pharmacol Ther 27:64–71, 1980.PubMedGoogle Scholar
  196. 196.
    Gibson JK, Somani P, Bassett AL: Electrophysiologic effects of encainide (MJ9067) on canine Purkinje fibers. Eur J Pharmacol 52:161–169, 1978.PubMedGoogle Scholar
  197. 197.
    Jackman WM, Zipes DP, Naccarelli GV, Rinkenberger RL, Heger JJ, Prystowsky EN: Electrophysiology of oral encainide. Am J Cardiol 49:1270–1279, 1982.PubMedGoogle Scholar
  198. 198.
    Roden DM, Reele SB, Higgins SB, Mayol RF, Gammans RE, Oates JA, Woosley RL: Total suppression of ventricular arrhythmias by encainide: pharmcokinetic and electrocardiographic characteristics. N Engl J Med 302:877–882, 1980.PubMedGoogle Scholar
  199. 199.
    Winkle RA, Peters F, Kates RE, Tucker C, Harrison DC: Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias. Circulation 64:290–296, 1981.PubMedGoogle Scholar
  200. 200.
    DiBanco R, Fletcher RD, Cohen AL, Gottdiener JS, Singh SN, Katz RJ, Mapp AF, Cockrell JL: Encainide treatment of chronic ventricular arrhythmia: a controlled prospective study. Circulation 64:IV-315, 1981.Google Scholar
  201. 201.
    Kesteloot H, Stroobandt R: Clinical experience of encanide (MJ9067): a new antiarrhythmic drug. Eur J Clin Pharmacol 16:323–329, 1979.PubMedGoogle Scholar
  202. 202.
    Elharrar V, Zipes DP: Effects of encainide and metabolites (MJ14030 and MJ9444) on canine cardiac Purkinje and ventricular fibers. J Pharmacol Exp Ther 220:440–447, 1982.PubMedGoogle Scholar
  203. 203.
    Sami M, Mason JW, Oh G, Harrison DC: Canine electrophysiology of encainide, a new anti-arrhythmic drug. Am J Cardiol 43:1149–1154, 1979.PubMedGoogle Scholar
  204. 204.
    Sami M, Mason JW, Peters F, Harrison DC: Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent. Am J Cardiol 44:526–532, 1979.PubMedGoogle Scholar
  205. 205.
    Carey EL Jr, Duff HJ, Roden DM, Primm RK, Oates JA, Woosley RL: Relative electrocardiographic and antiarrhythmic effects of encainide and its metabolites in man. Circulation 64:IV-264, 1981.Google Scholar
  206. 206.
    Woosley RL, Roden DM, Duff HJ, Carey EL, Wood AJJ, Wilkinson GR: Co-inheritance of deficient oxidative metabolism of encainide and debrisoquine. Clin Res 29:501A, 1981.Google Scholar
  207. 207.
    Koppe HG: The development of mexiletine. Postgrad Med J 53(Suppl I):22–24, 1977.PubMedGoogle Scholar
  208. 208.
    Singh BN, Vaughan Williams EM: Investigations of the mode of action a new antidysrhythmic drug (Ko 1173). Br J Pharmacol 44:1–9, 1972.PubMedGoogle Scholar
  209. 209.
    Yamaguchi I, Singh B, Mandel W: Electrophysiological actions of mexiletine on isolated rabbit atria and canine ventricular muscle and Purkinje fiber. Cardiovasc Res 13:288–296, 1979.PubMedGoogle Scholar
  210. 210.
    Weld FM, Bigger JT, Swistel D, Bordiuk J, Lau YH:Electrophysiological effects of mexiletine (Ko 1173) on ovine cardiac Purkinje fibers. J Pharmacol Exp Ther 210:222–228, 1979.PubMedGoogle Scholar
  211. 211.
    Iwamura N, Shimizu T, Toyoshima H, Toyama T, Yamada K: Electrophysiological actions of a new antiarrhythmic agent on isolated preparations of the canine Purkinje fiber and ventricular muscle. Cardiology 61:329–340, 1976.Google Scholar
  212. 212.
    Carmeliet E: Mechanisms of arrhythmias and of antiarrhythmic activity with special reference to mexiletine. Acta Cardiol (Suppl) 25:5–25, 1980.Google Scholar
  213. 213.
    Vaughan Williams EM: Mexiletine in isolated tissue models. Postgrad Med J (Suppl I) 53:30–34, 1977.Google Scholar
  214. 214.
    Harper RW, Olsson SB, Varnauskas E: Effect of mexiletine on monophasic acton potentials recorded from the right ventricle in man. Cardiovasc Res 13:303–310, 1979.PubMedGoogle Scholar
  215. 215.
    Danneberg PB, Shelley JH: The pharmacology of mexiletine. Postgrad Med J 53(Suppl I):25–29, 1979.Google Scholar
  216. 216.
    Roos JC, Paalman DCA, Dunning AJ: Electrophysiological effects of mexiletine in man. Postgrad Med J 53(Suppl I): 92–94, 1977.PubMedGoogle Scholar
  217. 217.
    McComish M, Robinson C, Kitson D, Jewitt DE: Clinical electrophysiological effects of mexiletine. Postgrad Med J 53(Suppl I):85–91, 1977.PubMedGoogle Scholar
  218. 218.
    Saunamaki KI: Haemodynamic effects of a new antiarrhythmic agent, mexiletine (Ko 1173) in ischemic heart disease, Cardiovasc Res 9:788–792, 1975.PubMedGoogle Scholar
  219. 219.
    Pozenel H: Hemodynamic studies on mexiletine, a new antiarrhythmic agent. Postgrad Med J 53(Suppl I): 78–80, 1977.PubMedGoogle Scholar
  220. 220.
    Shaw TRD: The effect of mexiletine on left ventricular ejection: a comparison with lidocaine and propranolol. Postgrad Med J 53 (Suppl I):69–73, 1977.PubMedGoogle Scholar
  221. 221.
    Prescott LF, Pottage A, Clements JF: Absorption, distribution and elimination of mexiletine. Postgrad Med J 53(Suppl I):50–55, 1977.PubMedGoogle Scholar
  222. 222.
    Kiddie MA, Kaye CM, Turner P, Shaw TRD: The influence of urinary pH on the elimination of mexiletine. Br J Clin Pharmacol 1:229–232, 1974.Google Scholar
  223. 223.
    Clark RA, Julian DG, Nimmo J, Prescott LF, Talbot R: Clinical pharmacological studies of Ko 1173 - a new antiarrhythmic agent. Br J Pharmacol 47:622–623, 1973.Google Scholar
  224. 224.
    Prescott LF, Adjepon-Yamoah KK, Talbot RG: Impaired metabolism of lignocaine in patients with myocardial infarction and cardiac failure. Br Med J 1:939–941, 1976.PubMedGoogle Scholar
  225. 225.
    Beckett AH, Chidomere EC: The distribution, metabolism and excretion of mexiletine in man. Postgrad Med J 53(Suppl I):60–66, 1977.PubMedGoogle Scholar
  226. 226.
    Johnston A, Burgess CD, Warrington SJ, Wadsworth J, Hamer NAJ: The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers. Br J Clin Pharmacol 8:349–352, 1979.PubMedGoogle Scholar
  227. 227.
    Talbot RG, Julian DG, Prescott LF: Long-term treatment of ventricular arrhythmias with oral mexiletine. Am Heart J 91:58–65, 1976.PubMedGoogle Scholar
  228. 228.
    Merrit HH, Putnam TJ: Sodium diphenylhydantoin in treatment of convulsive disorders. J Am Med Assoc 111: 1068–1073, 1938.Google Scholar
  229. 229.
    Harris AS, Kokernot RH: Effects of diphenylhydantoin sodium (dilantin sodium) and phenobarbital sodium uponectopic ventricular tachycardia in acute myocardial infarction. Am J Physiol 163:505–516, 1950.PubMedGoogle Scholar
  230. 230.
    Mosey L, Tyler MD: The effects of diphenylhydantoin sodium (dilantin), procaine hydrochloride, procaine amide, hydrochloride and quinidine hydrochloride upon ouabain-reduced ventricular tachycardia in unanesthetized dogs. Circulation 10:65–70, 1964.Google Scholar
  231. 231.
    Coveno BG, Wright R, Charleson DA: Effectiveness of several antifibrillatory drugs in the hypothermic dog. Am J Physiol 181:54–58, 1955.Google Scholar
  232. 232.
    Scherf D, Blumenfeld S, Taner D, Yieldiz M: The effect of diphenylhydantoin (dilantin) sodium on atrial flutter and fibrillation provoked by focal application of aconitine and delphinine. Am Heart J 60:936–947, 1960.PubMedGoogle Scholar
  233. 233.
    Helfant RH, Scherlag BJ, Damato AN: The electrophysiological properties of diphenylhydantoin sodium as compared to procaine amide in the normal and digitalis-intoxicated heart. Circulation 36:108–118, 1967.PubMedGoogle Scholar
  234. 234.
    Leonard WA: The use of diphenylhydantoin (dilantin) sodium in the treatment of ventricular tachycardia. Arch Intern Med 101:714–717, 1958.Google Scholar
  235. 235.
    Jensen RA, Katzung BG: Electrophysiological actions of diphenylhydantoin on rabbit atria. Circ Res 26:17–27, 1970.PubMedGoogle Scholar
  236. 236.
    Katzung BG, Jensen RA: Depressant action of diphenylhydantoinon electrical and mechanical properties of isolated rabbit and dog atria: Dependence on sodium and potassium. Am Heart J 80:80–88, 1970.PubMedGoogle Scholar
  237. 237.
    Rosen MR, Danilo P Jr, Alonso MB, Pippenger CE: Effects of therapeutic concentrations of diphenylhydantoin on transmembrane potentials of normal and depressed Purkinje fibers. J Pharmacol Exp Ther 197:594–604, 1974.Google Scholar
  238. 238.
    Bigger JT, Strauss HC, Bassett AL, Hoffman BF: Electrophysiological effects of diphenylhydantoin on canine Purkinje fibers. Circ Res 22:221–236, 1968.PubMedGoogle Scholar
  239. 239.
    Strauss HC, Bigger JT, Bassett AL, Hoffman BF: Actions of diphenylhydantoin on the electrical properties of isolated rabbit and canine atria. Circ Res 23:463–477, 1968.PubMedGoogle Scholar
  240. 240.
    Bassett AL, Bigger JT Jr, Hoffman BF: ‘Protective’ action of diphenylhydantoin on canine Purkinje fibers during hypoxia. J Pharmacol Exp Ther 173:336–343, 1970.PubMedGoogle Scholar
  241. 241.
    Bigger JT Jr, Weinberg DI, Kovalik ATW, Harris PD, Cranefield PF, Hoffman BF: Effects of diphenylhydantoin on excitability and automaticity of canine heart. Circ Res 26:1–13, 1970.PubMedGoogle Scholar
  242. 242.
    Rosati RA, Alexander JA, Schaal SF, Wallace AG: Influence of diphenylhydantoin on electrophysiological properties of the canine heart. Circ Res 21:757–765, 1967.PubMedGoogle Scholar
  243. 243.
    Gillis RA, McClellan JR, Sauer TS, Standaert FG: Depression of cardiac sympathetic nerve activity diphenylhydantoin. J Pharmacol Exp Ther 179:599–610, 1971.PubMedGoogle Scholar
  244. 244.
    Evans DE, Gillis RA: Effect of diphenylhydantoin and lidocanine on cardiac arrhythmias induced by hypothalmic stimulation. J Pharmacol Exp Ther 191:506–517, 1974.PubMedGoogle Scholar
  245. 245.
    Unger AH, Sklaroff HJ: Fatalities following intravenous use of sodium diphenylhydantoin for cardiac arrhythmias. Report of two cases. J Am Med Assoc 200:335–336, 1967.Google Scholar
  246. 246.
    Louis S, Kutt H, McDowell F: The cardiocirculatory changes caused by intravenous dilantin and its solvent. Am Heart J 74:523–529, 1967.PubMedGoogle Scholar
  247. 247.
    Russell JM, Harvey SC: Effects of diphenylhydantoin on canine atria and A-V conducting system. Arch Int Pharmacodyn Ther 182:219–231, 1969.PubMedGoogle Scholar
  248. 248.
    Caracta AR, Damato AN, Josephson ME, Ricciutti MA, Gallagher JJ, Lau SH: Electrophysiologic properties of diphenylhydantoin. Circulation 47:1234–1241, 1973.PubMedGoogle Scholar
  249. 249.
    Bigger JR Jr, Schmidt DH, Kutt H: Relationship between the plasma level of diphenylhydantoin sodium and its cardiac antiarrhythmic effects. Circulation 38:363–374, 1968.PubMedGoogle Scholar
  250. 250.
    Damato AN, Berkowitz WD, Patton RD, Lau SH: The effect of diphenylhydantoin on atrioventricular and intraventricular conduction in man. Am Heart J 79:51–56, 1970.PubMedGoogle Scholar
  251. 251.
    Dhatt MS, Gomes JAC, Reddy CP, Akhtar M, Caracta AR, Lau SH, Damato AN: Effects of Phenytoin on refractoriness and conduction in the human heart. J Cardiol Pharmacol 1:3–18, 1979.Google Scholar
  252. 252.
    Bissett JK, DeSoyza NDB, Kane JJ, Murphy ML: Improved intraventricular conduction of premature beats after diphenylhydantoin. Am J Cardiol 33:493–497, 1974.PubMedGoogle Scholar
  253. 253.
    Mixter CG III, Moran JM, Austen WG: Cardiac and peripheral vascular effects of diphenylhydantoin sodium. Am J Cardiol 17:332–338, 1966.PubMedGoogle Scholar
  254. 254.
    Lieberson AD, Schumacher RR, Childress RH, Boyd DL, Williams JF Jr: Effect of diphenylhydantoin on left ventricular function in patients with heart disease. Circulation 36:692–699, 1967.PubMedGoogle Scholar
  255. 255.
    Puri PS: The effect of diphenylhydantoin sodium (dilantin) on myocardial contractility and hemodynamics. Am Heart J 82:62–68, 1971.PubMedGoogle Scholar
  256. 256.
    Wilensky AJ, Lowden JA: Inadequate serum levels after intramuscular administration of diphenylhydantoin. Neurology 23:318–324, 1973.PubMedGoogle Scholar
  257. 257.
    Kutt H, Winters W, Kokenge R, McDowell F: Diphenylhydantoin metabolism blood levels and toxicity. Arch Neurol 11:642–648, 1964.PubMedGoogle Scholar
  258. 258.
    Dill WA, Kazenko A, Wolf LA, Glazko AJ: Studies on 5, 5’-diphenylhydantoin (dilantin) in animals and man. J Pharmacol Exp Ther 118:270–279, 1956.PubMedGoogle Scholar
  259. 259.
    Kutt H: Biochemical and genetic factors regulating dilantin metabolism in man. Ann NY Acad Sci 179:704–722, 1971.Google Scholar
  260. 260.
    Butler TC: Metabolic conversion of 5–5-diphenylhydantoin to 5’-(phydroxyphenyl)-5 phenylhydantoin. J Pharmacol Exp Ther 119:1–11, 1957.PubMedGoogle Scholar
  261. 261.
    Maynert EW: The metabolic fate of diphenylhydantoin in the dog, rat and man. J Pharmacol Exp Ther 130:275–284, 1960.PubMedGoogle Scholar
  262. 262.
    Kutt H, Haynes J, McDowell F: Some causes of ineffectiveness of diphenylhydantoin. Arch Neurol 14:489–492, 1966.PubMedGoogle Scholar
  263. 263.
    Bigger JT Jr: A method for the estimation of plasma diphenylhydantoin concentration. Am Heart J 77:572–573, 1969.PubMedGoogle Scholar
  264. 264.
    Gerber N, Wagner JG: Explanation of dose-dependent decline of diphenylhydantoin plasma levels by fitting to the integrated form of the Michaelis-Menten equation. Res Commun Chem Pathol Pharmacol 3:455–466, 1972.PubMedGoogle Scholar
  265. 265.
    Arnold K, Gerber N: The rate of decline of diphenylhydantoin in human plasma. Clin Pharmacol Ther 11:121–134 1970.PubMedGoogle Scholar
  266. 266.
    Atkinson AJ, Shaw JJ: Pharmacokinetic study of a patient with diphenylhydantoin toxicity. Clin Pharmacol Ther 14:521–528, 1973.PubMedGoogle Scholar
  267. 267.
    Kutt H, Verebely K: Metabolism of diphenylhydantoin by rat liver microsomes I. Characteristics of the reaction. Biochem Pharmacol 19:675–680, 1970.PubMedGoogle Scholar
  268. 268.
    Gerber N, Weller WL, Lynn R, Rangno RE, Sweetman BJ, Bush MT: Study of dose-dependent metabolism of 5,5-diphenylhydantoin in the rat using new methodology for isolation and quantitation of metabolites in vivo and in vitro. J Pharmacol Exp Ther 178:567–579, 1971.PubMedGoogle Scholar
  269. 269.
    Kutt H, Winters W, Scherman R, McDowell F: Diphenylhydantoin and phenobarbital toxicity; the role of liver disease. Arch Neurol 11:649–656, 1964.PubMedGoogle Scholar
  270. 270.
    Kutt H, Wolk M, Scherman R, McDowell F: Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology 14:542–548, 1964.PubMedGoogle Scholar
  271. 271.
    Cucinelli SA, Conney AH, Sansur M, Burns JJ: Drug interactions in man. I. Lowering effect of phenbarbital on plasma levels of bishyoroxycoumarin (dicumarol) and diphenylhydantoin (dilantin). Clin Pharmacol Ther 6:420–429, 1965.Google Scholar
  272. 272.
    Kutt H, Haynes J, Verebely K, McDowell F: The effect of phenobarbital on plasma diphenylhydantoin level and metabolism in man and in rat liver microsomes. Neurology 19:611–616, 1969.PubMedGoogle Scholar
  273. 273.
    Odar-Cederhof I, Borga O: Kinetics of DPH in uraemic patients: Consequences of decreased plasma protein binding. Eur J Clin Pharmacol 7:31–37, 1974.Google Scholar
  274. 274.
    Reidenberg M, Odar-Cederlof I, Bahr Von C, Borga O, Sjogvist F: Protein binding of DPH and desmethylimipramine in plasma from patients with poor renal function. N Engl J Med 285:264–267, 1971.PubMedGoogle Scholar
  275. 275.
    Sparberg M: Diagnostically confusing complications of DPH therapy. Ann Intern Med 59:914–930, 1963.PubMedGoogle Scholar
  276. 276.
    The Norwegian Multicenter Study Group: Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 304:801–807, 1981.Google Scholar
  277. 277.
    Wit AL, Hoffman BF, Rosen MR: Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiologic effect of beta adrenergic receptor stimulation and blockade. Part A. Am Heart J 90:521–533, 1975.PubMedGoogle Scholar
  278. 278.
    Black JW, Crowther AF, Shanks RG, Smith LH, Dornhurst AC: A new beta-receptor antagonist. Lancet 1:1080–1081, 1964.PubMedGoogle Scholar
  279. 279.
    Conolly ME, Kersting F, Dollery CT: The clinical pharmacology of beta-adrenoceptor blocking drug. Prog Cardiovasc Dis 19:203–234, 1976.PubMedGoogle Scholar
  280. 280.
    Davis LD, Temte JV: Effects of propranolol on the transmembrane potentials of ventricular muscle and Purkinje fibers in the dog. Circ Res 22:661–677, 1968.PubMedGoogle Scholar
  281. 281.
    Wit AL, Hoffman BF, Rosen MR: Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiologic effects of beta adrenergic receptor stimulation and blockade. Part C. Am Heart J 90:795–803, 1975.PubMedGoogle Scholar
  282. 282.
    Pitt WA, Cox AR: The effect of the β-adrenergic antagonist propranolol on rabbit atrial cells with the use of the ultramicroelectrode technique. Am Heart J 76:242, 1968.PubMedGoogle Scholar
  283. 283.
    Papp JG, Vaughan Williams SM: A comparison of the anti-arrhythmic action of ICI 50172 and (-) propranolol and their effects on intracellular cardiac action potentials and other features of cardiac function. Br J Pharmacol 36:391–398, 1969.Google Scholar
  284. 284.
    Tarr M, Luckstead EF, Jurewicz PA, Haas HG: Effect of propranolol on the fast inward sodium current in frog atrial muscle. J Pharmacol Exp Ther 184:599–610, 1973.PubMedGoogle Scholar
  285. 285.
    Wu CH, Narahashi T: Mechanism of action of propranolol on squid axon membranes. J Pharmacol Exp Ther 184: 155–162, 1973.PubMedGoogle Scholar
  286. 286.
    Woosley RL, Kornhauser D, Smith R, Reele S, Higgins SB, Nies AS, Shand DG, Oates TA: Suppression of chronic ventricular arrhythmias with propranolol. Circulation 60:819–827, 1979.PubMedGoogle Scholar
  287. 287.
    Carmeliet E, Vereeke J: Adrenaline and the plateau phase of the cardiac action potential. Eur J Physiol 313:300–315, 1969.Google Scholar
  288. 288.
    Pappano AJ: Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circ Res 27:379–390, 1970.PubMedGoogle Scholar
  289. 289.
    Harrison LA, Wittig J, Wallace AG: Adrenergic influences on the distal Purkinje system of the canine heart. Circ Res 32:329–339, 1973.PubMedGoogle Scholar
  290. 290.
    Koerpel BJ, Davis LD: Effects of lidocaine, propranolol and sotalol on ouabain-induced changes in transmembrane potential of canine Purkinje fibers. Circ Res 30:681, 1972.PubMedGoogle Scholar
  291. 291.
    Hewett K, Rosen MR: β adrenergic modulation of delayed afterdepolarizations. Am J Cardiol 49:913, 1982.Google Scholar
  292. 292.
    Lucchesi BR, Whitsitt LS: The pharmacology of beta-adrenergic blocking agents. Prog Cardiovasc Dis 11:410–430, 1969.PubMedGoogle Scholar
  293. 293.
    Wallace AG, Troyer WG, Lesage MA, Zotti EF: Electrophysiologic effects of isoproterenol and beta blocking agents in awake dogs. Circ Res 18:140–148, 1966.Google Scholar
  294. 294.
    Epstein SE, Robinson BF, Kahler RL, Braunwald E: Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man. J Clin Invest 44:1745–1753, 1965.PubMedGoogle Scholar
  295. 295.
    Sowton E: Hemodynamic changes after beta adrenergic blockade. Am J Cardiol 18:317–320, 1966.PubMedGoogle Scholar
  296. 296.
    Parker JO, West RO, Digiorgi S: Hemodynamic effects of propranolol in coronary heart disease. Am J Cardiol 21: 11–19, 1968.PubMedGoogle Scholar
  297. 297.
    Dwyer EM, Wiener L, Cox JW: Effects of beta-adrenergic blockade on left ventricular hemodynamics and the electrocardium during exercise induced angina pectoris. Circulation 38:250–260, 1968.PubMedGoogle Scholar
  298. 298.
    Wolfson S, Gorlin R: Cardiovascular pharmacology of propranolol in man. Circulation 40:501–511, 1969.PubMedGoogle Scholar
  299. 299.
    Stern S, Eisenberg S: The effect of propranolol (inderal) on the electrocardiogram of normal subjects. Am Heart J 77:192–195, 1969.PubMedGoogle Scholar
  300. 300.
    Gibson D, Sowton E: The use of beta-adrenergic receptor blocking drugs in dysrhythmias. Prog Cardiovasc Dis 12:16–39, 1969.PubMedGoogle Scholar
  301. 301.
    Morgan TO, Sabto J, Anavekar SM, Louis WJ, Doyle AE: A comparison of beta adrenergic blocking drugs in the treatment of hypertension. Postgrad Med J 50:253–259, 1974.Google Scholar
  302. 302.
    Gradman AH, Winkle RA, Fitzgerald JW, Meffin PJ, Stoner J, Bell PA, Harrison DC: Suppression of premature ventricular contractions by acebutolol. Circulation 55: 785–791, 1977.PubMedGoogle Scholar
  303. 303.
    LeClercq JF, Rosengarten MD, Kural S, Atturl P, Coumel P: Effects of intrinsic sympathetic activity of beta-blockers on SA and AV nodes in man. Eur J Cardiol 12:367–375, 1981.PubMedGoogle Scholar
  304. 304.
    Seides SF, Josephson ME, Batsford WP, Weisfogel GM, Lau SH, Damato AN: The electrophysiology of propranolol in man. Am Heart J 88:733–741, 1974.PubMedGoogle Scholar
  305. 305.
    Seipel L, Both G, Briethardt G, Gleichmann U, Loogen F: Actions of antiarrhythmic drugs on His bundle electrogram and sinus node function. Acta Cardiol (Suppl 18): 251–267, 1974.Google Scholar
  306. 306.
    Smithen CS, Balcon R, Sowton E: Use of His potentials to assess changes in atrioventricular conduction produced by a series of beta-adrenergic blocking agents. Br Heart J 33:955–961, 1971.PubMedGoogle Scholar
  307. 307.
    Berkowitz WD, Wit AL, Lau SH, Steiner C, Damato AN: Effects of propranolol on cardiac conduction. Circulation 40:855–862, 1969.Google Scholar
  308. 308.
    Priola DV: Effects of beta receptor stimulation and blockade on AV nodal and bundle branch conduction in the canine heart. Am J Cardiol 31:35–40, 1973.PubMedGoogle Scholar
  309. 309.
    Wu D, Denes P, Dhingra R, Kahn A, Rosen KM: The effects of propranolol on the induction of AV nodal reentrant paroxysmal tachycardia. Circulation 50:665–677, 1974.PubMedGoogle Scholar
  310. 310.
    Giudicelli JF, Lhoste F, Bossier JR: Beta-adrenergic blockade and atrioventricular conduction impairment. Eur J Pharmacol 31:216–225, 1975.PubMedGoogle Scholar
  311. 311.
    Rosen KM, Barwolf C, Ehsani A, Rahimtoola SH: Effects of lidocaine and propranolol on the normal and anomalous pathways in patients with preexcitation. Am J Cardiol 30:801–809, 1972.PubMedGoogle Scholar
  312. 312.
    Wellens H, Brugada P, Roy D, Weiss J, Bar F: Shortening of the period of the accessory pathway in the Wolff-Parkinson-White Syndrome by beta-adrenergic stimulation. Circulation 64 (Suppl IV):IV-145, 1981 (abstract).Google Scholar
  313. 313.
    Nies AS, Evans GH, Shand DG: Regional hemodynamic effects of beta-adrenergic blockade with propranolol in the unanesthetized primate. Am Heart J 85:97–102, 1973.PubMedGoogle Scholar
  314. 314.
    Sowton E, Smithen C, Leaver D, Barr L: Effects of practolol on exercise tolerance in patients with angina pectoris. Am J Med 51:63–70, 1971.PubMedGoogle Scholar
  315. 315.
    Stephen SA: Unwanted effects of propranolol. Am J Cardiol 18:463–468, 1966.PubMedGoogle Scholar
  316. 316.
    Vaughan Williams EM, Bagwell EE, Singh BN: Cardio-specificity of β-receptor blockade. Cardiovasc Res 7:226–240, 1973.Google Scholar
  317. 317.
    Fitzgerald JD: Perspectives in adrenergic beta-receptor blockade. Clin Pharmacol Ther 10:292–309, 1969.PubMedGoogle Scholar
  318. 318.
    Gibson DC: Pharmacodynamic properties of β-adrenergic receptor blocking drugs in man. Drugs 7:8–38, 1974.PubMedGoogle Scholar
  319. 319.
    Mason JW, Specter JM, Ingelo MB, Daughters GT, Ferris AC, Alderman EL: Haemodynamic effects of acebutolol. Br Heart J 40:29–34, 1978.PubMedGoogle Scholar
  320. 320.
    Robinson C, Jackson PG, Fisk C, Jewitt DE: Haemodynamic effects of atenelol in patients with coronary artery disease. Br Heart J 40:22–28, 1978.PubMedGoogle Scholar
  321. 321.
    Lewis CM, Brink AJ, Theron MJ, Kotze JCN: β-adrenergic blockage, hemodynamics and myocardial energy metabolism in patients with ischemic heart disease. Am J Cardiol 21:846–859, 1968.PubMedGoogle Scholar
  322. 322.
    Wit AL, Hoffman BF, Rosen MR: Electrophysiology and pharmacology of cardiac arrhythmias. Cardiac electrophysiologic effects of beta adrenergic receptor stimulation and blockade. Part B. Am Heart J 90:665–675, 1975.PubMedGoogle Scholar
  323. 323.
    Shand DG, Nuckolls EM, Oates JA: Plasma propranolol levels in adults, with observations in four children. Clin Pharmacol Ther 11:112–120, 1970.PubMedGoogle Scholar
  324. 324.
    Woosley RL, Shand DG, Kornhauser DM, Nies AS, Oates JA: Relation of plasma concentration and dose of propranolol to its effect on resistant ventricular arrhythmias. Clin Res 25:262A, 1977 (abstract).Google Scholar
  325. 325.
    Coltark DJ, Shand DG: Plasma propranolol levels in the quantitative assessment of β-adrenergic blockade in man. Br Med J 3:731–735, 1970.Google Scholar
  326. 326.
    Evans GH, Shand DG: Disposition of propranolol. IV. Independent variation in steady state circulating drug concentration and half-life as a result of plasma drug binding in man. Clin Pharmacol Ther 14:494–500, 1973.PubMedGoogle Scholar
  327. 327.
    Nies AS, Shand DG: Clinical pharmacology of propranolol. Circulation 52:6–15, 1975.PubMedGoogle Scholar
  328. 328.
    Evans GH, Shand DG: Disposition of propranolol. V. Drug accumulation and steady state concentration during chronic oral administration in man. Clin Pharmacol Ther 14:487–493, 1973.PubMedGoogle Scholar
  329. 329.
    Shand DG, Rangno RE: The disposition of propranolol. Elimination during oral absorption in man. Pharmacology 7:159–168, 1972.PubMedGoogle Scholar
  330. 330.
    Hayes A, Cooper RG: Studies on the absorption, distribution, and excretion of propranolol in rat, dog, and monkey. J Pharmacol Exp Ther 176:302–311, 1971.PubMedGoogle Scholar
  331. 331.
    Walle T, Ishizaki T, Gaffney TE: Isopropylamine, a biologically active deamination product of propranolol in dogs: identification of deuterated and unlabeled isopropylamine by gas chromatography - mass spectrometry. J Pharmacol Exp Ther 183:508–512, 1972.PubMedGoogle Scholar
  332. 332.
    Walle T, Gaffney TE: Propranolol metabolism in man and dog. Mass spectrometric identification of six new metabolites. J Pharmacol Exp Ther 182:83–92, 1972.PubMedGoogle Scholar
  333. 333.
    Cleaveland CR, Shand DG: Effect of route of administration on the relationship between beta-adrenergic blockade and plasma propranolol level. Clin Pharmacol Ther 13: 181–185, 1972.PubMedGoogle Scholar
  334. 334.
    Fitzgerald JD, O’Donnell SR: Pharmacology of 4-hydroxy-propranolol a metabolite of propranolol. Br J Pharmacol 43:222–235, 1971.PubMedGoogle Scholar
  335. 335.
    Walle T, Ishizaki T, Sachens D, Privitera D, Garteiz D, Gaffney TE: Propranolol metabolism in man. Pharmacological properties of new metabolites. In: Acheson GH (ed) Abstracts of invited presentations. Fifth Int Cong Pharmacol, San Francisco, 1972, p 74.Google Scholar
  336. 336.
    Ishizaki T, Privitera PJ, Walle T, Gaffney TE: Cardiovascular actions of a new metabolite of propranolol: isopropylamine. J Pharmacol Exp Ther 189:626–632, 1974.PubMedGoogle Scholar
  337. 337.
    Saelens DA, Walle T, Privitera PJ, Knapp DR, Gaffney TE: Central nervous system effects and metabolic disposi-tion of a glycol metabolite of propranolol. J Pharmacol Exp Ther 188:86–92, 1974.PubMedGoogle Scholar
  338. 338.
    Evans GH, Shand DG: Disposition of propranolol. VI. Independent variation in steady-state circulating drug concentrations and half-life as a result of plasma drug binding in man. Clin Pharmacol Ther 14:494–500, 1973.PubMedGoogle Scholar
  339. 339.
    Nies AS, Evans GH, Shand DG: The hemodynamic effects of beta adrenergic blockade on the flow-dependent hepatic clearance of propranolol. J Pharmacol Exp Ther 184:716–721, 1973.PubMedGoogle Scholar
  340. 340.
    Thompson F, Jaekes AM, Faulkes DM: Pharmacodynamics of propranolol in renal failure. Br Med J 2:434–436, 1972.PubMedGoogle Scholar
  341. 341.
    Lowenthal DT, Briggs WA, Gibson TP, Nelson H, Arksena WJ: Pharmakokinetics of oral propranolol in chronic renal disease. Clin Pharmacol Ther 16:761–769, 1974.PubMedGoogle Scholar
  342. 342.
    Ablad B, Ervik M, Hallgren J, Johnsson G, Solvell L: Pharmacological effects and serum levels of orally administered alprenolol in man. Eur J Clin Pharmacol 5:44–52, 1972.Google Scholar
  343. 343.
    Riess W, Rajagopalan TG, Imhof P, Schmid K, Keberle H: Metabolic studies on oxprenolol in animals and man by means of radio-tracer techniques and GLC analysis. Postgrad Med J 46(Suppl):32–39, 1970.Google Scholar
  344. 344.
    Johansson R, Regaroth CG, Sjorgren J: Absorption of alprenolol in man from tablets with different rates of release. Acta Pharm Suec 8:59–70, 1971.PubMedGoogle Scholar
  345. 345.
    Carruthers SG, Kelly JG, McDevitt DG, Shanks RG: Blood levels of practolol: oral and parenteral administration and their relationship to exercise heart rate. Clin Pharmacol Ther 15:497–509, 1974.PubMedGoogle Scholar
  346. 346.
    Gugler R, Herold W, Dengler HJ: Pharmcokinetics of pindolol in man. Eur J Clin Pharmacol 7:17–34, 1974.PubMedGoogle Scholar
  347. 347.
    Johnsson G, Regaroth CG: Clinical pharmcokinetics of beta-adrenoreceptor blocking drugs. Drugs II (Suppl 1): 111–121, 1976.Google Scholar
  348. 348.
    Riess W, Rajagopalan TG, Imhof P, Schmid K, Keberele H: Metabolic studies on oxprenolol in animals and man by means of radio-tracer techniques and GLC analysis. Postgrad Med J 46 (Suppl):32–39, 1970.Google Scholar
  349. 349.
    Alderman EL, Coltart DJ, Weltach GE, Harrison DC: Coronary artery syndromes after sudden propranolol withdrawal. Ann Intern Med 81:625–627, 1974.PubMedGoogle Scholar
  350. 350.
    Miller RR, Olson HG, Amsterdam EA, Mason DT: Propranolol withdrawal rebound phenomenon: exacerbation of coronary events after abrupt cessation of anti-anginal therapy. N Engl J Med 293:416–418, 1975.PubMedGoogle Scholar
  351. 351.
    Frishman WH, Christodoulou J, Weksler B, Smithen C, Killip J, Scheidt S: Abrupt propranolol withdrawal in angina pectoris: effects on platelet aggregation and exercise tolerance. Am Heart J 95:169–179, 1978.PubMedGoogle Scholar
  352. 352.
    Connolly CK, Batten JC: Comparison of the effect of alprenolol and propranolol on specific airway conductance in asthmatic patients. Br Med J 2:515–516, 1970.PubMedGoogle Scholar
  353. 353.
    Skinner C, Palmer KNV, Kerridge DF: Comparison of the effects of acebutolol and practolol in airways obstruction in asthmatics. Br J Clin Pharmacol 2:417, 1972.Google Scholar
  354. 354.
    Formgren H, Eriksson ME: Effects of practolol in combination with terbutaline in the treatment of hypertensionand arrhythmias in asthmatic patients. Scand J Resp Dis 56:217–222, 1975.Google Scholar
  355. 355.
    Skinner C, Gaddo J, Palmer KNV: Comparison of effects of metoprolol and propranolol on asthmatic airway obstruction. Br Med J 1:504, 1976.PubMedGoogle Scholar
  356. 356.
    Singh BN, Whitlock RML, Combes RH, Williams FH, Harris EA: Effects of cardioselective β-adrenoceptor blockade on specific airways resistance in normal subjects and in patients with bronchial asthma. Clin Pharmacol Ther 19:493–501, 1976.PubMedGoogle Scholar
  357. 357.
    Wright P: Untoward effect associated with practolol administration: oculomucocutaneous syndrome. Br Med J 1:595–598, 1975.PubMedGoogle Scholar
  358. 358.
    Felix RH, Ive FA, Dahl MCG: Cutaneous and ocular reactions to practolol. Br Med J 4:321, 1974.PubMedGoogle Scholar
  359. 359.
    Cubey RB, Taylor SH: Ocular reactions to propranolol and resolution on continued treatment with a different beta blocking drug. Br Med J 4:327, 1973.Google Scholar
  360. 360.
    Harty RP: Sclerosing peritonitis and propranolol. Arch Intern Med 138:1424–1426, 1978.PubMedGoogle Scholar
  361. 361.
    Holt PJA, Waddington E: Oculocutaneous reaction to oxprenolol. Br Med J 2:539–540, 1975.PubMedGoogle Scholar
  362. 362.
    Knapp MS, Gallaway HR, Clayden JR: Ocular reactions to beta blockers. Br Med J 2:562, 1975.Google Scholar
  363. 363.
    Windsor WP, Durrein F, Dyer NH: Fibrinous peritonits: a complication of practolol therapy. Br Med J 2:68, 1975.PubMedGoogle Scholar
  364. 364.
    Status report on beta-blockers. FDA Drug Bull 8:13, 1978.Google Scholar
  365. 365.
    Haas H, Hartfelder G: α-Isopropyl-α(N-methyl-N-homoveratryl-α-amino propyl)-3–4-dimethoxyphenyl acetonstrol, eine Substanz mit Coronäsgefäss-Eigenschaften. Arzneimittel-forsch 12:549–558, 1962.Google Scholar
  366. 366.
    Fleckenstein A, Doring HJ, Kammermaier H: Einfluss von beta-receptor Entblocker und verwandten Substanzen auf Erregung, Kontraktion und Energiestoffwechsel des Myokordifasers. Klin Wochenschr 46:343, 1968.PubMedGoogle Scholar
  367. 367.
    Nayler WG, McInnes I, Swann JP, Price JM, Carson V, Race D, Lowe TE: Some effects of iproveratril (isoptin) on the cardiovascular system. J Pharmacol Exp Ther 161:247, 1968.PubMedGoogle Scholar
  368. 368.
    Kohlhardt M, Bauer B, Krause H, Fleckenstein A: Differentiation of the transmembrane Na + Ca channels in mammalian cardiac fibers by the use of specific inhibitors. Pflugers Arch 335:309–322, 1972.PubMedGoogle Scholar
  369. 369.
    Tritthart H, Fleckenstein B, Fleckenstein A: Some fundamental actions of antiarrhythmic drugs on the excitability and the contractility of single myocardial fibers. Arch Pharmacol 269:212, 1971.Google Scholar
  370. 370.
    Rosen MR, Ilvento JP, Gelband H, Merker C: Effects of verapamil on electrophysiologic properties of canine Purkinje fibers. J Pharmacol Exp Ther 189:414–421, 1974.PubMedGoogle Scholar
  371. 371.
    Cranefield PF, Aronson RS and Wit AL: Effect of verapamil on the normal action potential and on a calcium-dependent slow response of canine Purkinje fibers. Circ Res 34:204–213, 1974.PubMedGoogle Scholar
  372. 372.
    Wit AL, Cranefield P: Effect of verapamil on the sinoatrial and atrioventricular nodes of the rabbit and the mechanism by which it arrests reentrant atrioventricular nodal tachycardia. Circ Res 35:413–425, 1974.PubMedGoogle Scholar
  373. 373.
    Singh BN, Vaughan Williams EM: A fourth class of anti-dysrhythmic action? Effect of verapamil on ouabain toxicity, on atrial and ventricular intracellular potentials, and on other features of cardiac function. Cardiovasc Res 6:109–119, 1972.PubMedGoogle Scholar
  374. 374.
    Rosen MR, Wit AL, Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias. VI Cardiac effects of verapamil. Am Heart J 89:665–673, 1975.PubMedGoogle Scholar
  375. 375.
    Danilo P Jr, Hordof AJ, Reder RF, Rosen MR: Effects of verapamil on electrophysiologic properties of blood superfused cardiac Purkinje fibers. J Pharmacol Exp Ther 213:222–227, 1980.PubMedGoogle Scholar
  376. 376.
    Bayer R, Kalusche D, Kaufmann R, Manhold R: Inotropic and electrophysiological actions of verapamil and D600 in mammalian myocardium. III. Effects of the optical isomers on transmembrane action potentials. Naunyn Schmiedebergs Arch Pharmacol 290:81–97, 1975.PubMedGoogle Scholar
  377. 377.
    Hordof AJ, Edie R, Malm JR, Hoffman BF, Rosen MR: Electrophysiological properties and response to pharmacologic agents of fibers from diseased human atria. Circulation 54:774–779, 1976.PubMedGoogle Scholar
  378. 378.
    Spear JF, Horowitz LN, Moore EN: The slow response in human ventricle. In: Zipes DP, Bailey JC, Elharrar V (eds) The Slow Inward Current and Cardiac Arrhythmias. Martinus Nijhoff, The Hague, 1980, pp 309–326.Google Scholar
  379. 379.
    Kohlhardt M, Muich Z: Studies on the inhibitory effect of verapamil on the slow inward current in mammalian ventricular myocardium. J Mol Cell Cardiol 10:1037–1052, 1978.PubMedGoogle Scholar
  380. 380.
    Kass RS, Tsien R: Multiple effects for calcium antagonists on plateau currents in cardiac Purkinje fibers. J Gen Physiol 66:109–119, 1972.Google Scholar
  381. 381.
    Gettes LS, Saito T: Effect of antiarrhythmic drugs on the slow inward current system. In: Zipes DP, Bailey JC, Elharrar V (eds) The Slow Inward Current and Cardiac Arrhythmias. Martinus Nijhoff, The Hague, 1980, pp 455–477.Google Scholar
  382. 382.
    Wit AL, Wiggins JR, Cranefield PF: Some effects of electrical stimulation on impulse initiation in cardiac fibers: Its relevance for the determination of the mechanism of clinical cardiac arrhythmias. In: Wellens HJJ, Lie KI, Janse M (eds) The Conduction System of the Heart: Structure, Function and Clinical Implications. Lea and Febiger, Philadelphia, 1976, p 163.Google Scholar
  383. 383.
    Wit AL, Cranefield PF: Triggered and automatic activity in the canine coronary sinus. Circ Res 41:435–445, 1977.Google Scholar
  384. 384.
    Kass R, Tsien R, Weingart R: Ionic bases of transient inward current induced by strophanthidin in cardiac Purkinje fibers. J Physiol (Lond) 281:209–226, 1978.Google Scholar
  385. 385.
    Angus JA, Richmond DR, Dhumma-Upakorn LB, Cobbin LB, Goodman AA: Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility + atrioventricular conduction. Cardiovasc Res 10: 623–632, 1976.PubMedGoogle Scholar
  386. 386.
    Okada T: Effect of verapamil on electrical activities of SA node, ventricular muscle + Purkinje fibers in isolated rabbit hearts. Jpn Circ J 40:329–341, 1976.PubMedGoogle Scholar
  387. 387.
    Hirata Y, Kodama I, Iwamura N, Shimizu T, Toyama J, Yamada K: Effects of verapamil on canine Purkinje fibers and ventricular muscle fibers with particular reference tothe alternation of action potential duration after a sudden increase in driving rate. Cardiovasc Res 13:1–8, 1979.PubMedGoogle Scholar
  388. 388.
    Heng MK, Singh BN, Roche AHG, Norris RM, Mercer CJ: Effect of intravenous verapamil on cardiac arrhythmias and on the electrocardiogram. Am Heart J 90:487–498, 1975.PubMedGoogle Scholar
  389. 389.
    Neuss H, Schlepper M: Der Einfluss von Verapamil auf die atrioventrikulare Überleitung, Lokalisation des Wirkungsortes mit His Bundel Elektrogrammen. Verhandlungen der Deutschen Gesellschaft für Kreislaufforschung 37:433–438, 1971.PubMedGoogle Scholar
  390. 390.
    Krikler DM, Spurrell RAJ: Verapamil in the treatment of paroxysmal supraventricular tachycardia. Postgrad Med J 50:447–453, 1974.PubMedGoogle Scholar
  391. 391.
    Puech P: Dissection de la Conduction Sinoventriculaire pour l’étude du Verapamil injectable. Montpellier Centre Hospitalier, 1972.Google Scholar
  392. 392.
    Huisiani MH, Kvasnicka J, Ryden L, Holmberg S: Action of verapamil on sinus node, atrioventricular and intraventricular conduction. Br Heart J 35:734–737, 1973.Google Scholar
  393. 393.
    Wellens HJJ, Tan SL, Bar FWH, Düren DR, Lie KI, Dohmen HM: Effect of verapamil studied by programmed electrical stimulation of the heart in patients with paroxysmal reentrant SVT, Br Heart J 39:1058–1066, 1977.PubMedGoogle Scholar
  394. 394.
    Roy PR, Spurrell RAJ, Sowton E: The effect of verapamil on the cardiac conduction system in man. Postgrad Med J 50:270–275, 1974.Google Scholar
  395. 395.
    Nayler WG, Szeto J: Effect of verapamil on contractility, oxygen utilization and calcium exchange ability to mammalian heart muscle. Cardiovasc Res 6:120–128, 1972.PubMedGoogle Scholar
  396. 396.
    Smith HJ, Goldstein RA, Griffith JM, Kent KM, Epstein SE: Regional contractility: selective depression of ischemic myocardium by verapamil. Circulation 54:629–635, 1976.PubMedGoogle Scholar
  397. 397.
    Haeusler G: Differential effect of verapamil on excitation conduction coupling in smooth muscle and on excitation secretion coupling in adrenergic terminals. J Pharmacol Exp Ther 180:672–679, 1972.PubMedGoogle Scholar
  398. 398.
    Baky SH, Kirsten EB: Verapamil. In: Goldberg ME (ed) Pharmacological and Biochemical Properties of Drug Substances. Am Pharmaceut Assoc, Acad Pharmaceut Sci, Washington, 1981.Google Scholar
  399. 399.
    Hagemeijer F: Verapamil in the management of supraventricular tachyarrhythmias occurring after a recent myocardial infarction. Circulation 57:751–755, 1978.PubMedGoogle Scholar
  400. 400.
    Melville KI, Shister HE, Huq S: Iproveratril: experimental data on coronary-dilatation and anti-arrhythmic action. Can Med Assoc J 90:761–770, 1964.PubMedGoogle Scholar
  401. 401.
    Johnson SM, Mauritson DR, Hilles LD, Willerson JT: Verapamil in the treatment of Prinzmetals variant angina: a long term, double-blind, randomized trial. N Engl J Med 304:862–866, 1981.PubMedGoogle Scholar
  402. 402.
    Krikler D: Verapamil in cardiology. Eur J Cardiol 2:3–10, 1974.PubMedGoogle Scholar
  403. 403.
    Schomerus M, Spiegelhalder B, Stieren B, Eichelbaum M: Physiological disposition of verapamil in man. Cardiovasc Res 10:605–612, 1976.PubMedGoogle Scholar
  404. 404.
    Schlepper M, Thormann J, Schwarz F: The pharmacodynamics of orally taken verapamil and verapamil retard as judged by their negative dromotropic effects. Arzneim Forsch 25:1452–1455, 1975.Google Scholar
  405. 405.
    Neugebauer G: Comparative cardiovascular actions of verapamil and its major metabolites in the anesthetized dog. Cardiovasc Res 12:247–254, 1978.PubMedGoogle Scholar
  406. 406.
    Woodcock BG, Rietbrock I, Vohringer HF, Rietbrock N: Verapamil disposition in liver disease and intensive-care patients: kinetics clearance and apparent blood flow relationships. Clin Pharmacol Ther 29:27–34, 1981.PubMedGoogle Scholar
  407. 407.
    Investigator’s brochure. Isoptin (verapamil hydrochloride). Knoll Pharmaceutical Co.Google Scholar
  408. 408.
    Kesteloot H: General aspects of antiarrhythmic treatment with aprindine. Acta Cardiol [Suppl] (Brux) 18:303–316, 1974.Google Scholar
  409. 409.
    Kesteloot H, Van Mieghem W, DeGeest H: Aprindine (AC 1802) a new antiarrhythmic drug. Acta Cardiol (Brux) 28:145–165, 1973.Google Scholar
  410. 410.
    Carmeliet E, Verdonck F: Effects of aprindine and lidocaine on transmembrane potentials and radioactive K efflux in different cardiac tissues. Acta Cardiol [Suppl] (Brux) 18:73–90, 1974.Google Scholar
  411. 411.
    Verdonck F, Vereecke J, Vleugels A: Electrophysiological effects of aprindine on isolated heart preparations. Eur J Pharmacol 26:338–347, 1974.PubMedGoogle Scholar
  412. 412.
    Steinberg MI, Greenspan K: Intracellular electrophysiological alterations in canine cardiac conducting tissue induced by aprindine and lidocaine. Cardiovasc Res 10:236–244, 1976.PubMedGoogle Scholar
  413. 413.
    Elharrar V, Bailey JC, Lathrop DA, Zipes DP: Effects of aprindine on slow channel action potentials and transient depolarizations in canine Purkinje fibers. J Pharmacol Exp Ther 205:410–417, 1978.PubMedGoogle Scholar
  414. 414.
    Gilmour RF Jr, Chikhavev VN, Jurevichus JA, Zacharov SI, Zipes DP, Rosenshtraukh LV: Effect of aprindine on transmembrane currents and contractile force in frog atria. J Pharmacol Exp Ther 217:390–396, 1981.PubMedGoogle Scholar
  415. 415.
    Reiser J, Freeman AR, Greenspan K: Aprindine-a calcium mediated antiarrhythmic. Fed Proc 33:476, 1974 (abstract).Google Scholar
  416. 416.
    Harker RJ, Greenspan K: Modification of calcium dependent slow responses in canine Purkinje fibers by aprindine. Fed Proc 36:946, 1977 (abstract).Google Scholar
  417. 417.
    Georges A, Hosslet A, Duvernay G: Pharmacological evaluation of aprindine (AC 1802). A new anti-arrhythmic agent. Acta Cardiol (Brux) 28:166–191, 1973.Google Scholar
  418. 418.
    Elharrar V, Foster PR, Zipes DP: Effects of aprindine HCl on cardiac tissues. J Pharmacol Exp Ther 195:201–205, 1975.PubMedGoogle Scholar
  419. 419.
    Seipel L, Both A, Breithardt G, Gleichmann U, Loogen F: Action of antiarrhythmic drugs on His bundle electrogram and sinus node function. Acta Cardiol [Suppl] (Brux) 18:251–267, 1974.Google Scholar
  420. 420.
    Breithardt G, Gleichmann V, Seipel L, Loogen F: Long term oral anti-arrhythmic therapy by antiarrhythmic drugs. Acta Cardiol [Suppl] (Brux) 18:341–353, 1974.Google Scholar
  421. 421.
    Schlepper M, Neuss H: Changes of refractory periods in the A-V conduction system induced by antiarrhythmic drugs. Acta Cardiol [Suppl] (Brux) 18:269–277, 1974.Google Scholar
  422. 422.
    Zipes DP, Gaum WE, Foster PR, Rosen KM, Wu D, Amat-y-Leon F, Noble RJ: Aprindine for treatment of supraventricular tachycardias. Am J Cardiol 40:586–596, 1977.PubMedGoogle Scholar
  423. 423.
    Piessens J, Willems J, Kesteloot H, DeGeest H: Effects ofaprindine on left ventricular contractility in man. Acta Cardiol [Suppl] (Brux) 18:203–216, 1971.Google Scholar
  424. 424.
    Rousseau MF, Brasseur LA, Detry JM: Hemodynamic effects of aprindine during upright exercise in normal subjects. Acta Cardiol [Suppl] (Brux) 18:195–201, 1974.Google Scholar
  425. 425.
    Remme WJ, Verdouw PD: Cardiovascular effects of aprindine, a new antiarrhythmic drug. Eur J Cardiol 314: 307–313, 1975.Google Scholar
  426. 426.
    Brutsaert DL: Effects of aprindine on myocardial contractility. Acta Cardiol [Suppl] (Brux) 18:91–99, 1974.Google Scholar
  427. 427.
    Fasola AF, Carmichael R: The pharmacology and clinical evaluation of aprindine, a new antiarrhythmic agent. Acta Cardiol [Suppl] (Brux) 18:317–333, 1974.Google Scholar
  428. 428.
    Fasola AF, Noble RJ, Zipes DP: Treatment of recurrent ventricular tachycardia and fibrillation with aprindine. Am J Cardiol 39:903–909, 1977.PubMedGoogle Scholar
  429. 429.
    Murphy PJ: Metabolic pathways of aprindine. Acta Cardiol [Suppl] (Brux) 18:131–142, 1974.Google Scholar
  430. 430.
    Kroll DA, Lucchesi BR: Antiarrhythmic and antifibrillatory properties of aprindine. J Pharmacol Exp Ther 194: 427–434, 1975.PubMedGoogle Scholar
  431. 431.
    Gaum WE, Elharrar V, Walker PD, Zipes DP: Influence of excitability of the ventricular fibrillation threshold in dogs. Am J Cardiol 40:929–935, 1977.PubMedGoogle Scholar
  432. 432.
    Elharrar V, Gaum WE, Zipes DP: Effects of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs. Am J Cardiol 39:544–549, 1977.PubMedGoogle Scholar
  433. 433.
    Leeuwen R van, Meyboom RHB: Agranulocytosis and aprindine. Lancet 2:1137, 1976.PubMedGoogle Scholar
  434. 434.
    Elewaut A, Van Durme JP, Goethals L, Kauffman JM, Mussche M, Elinck W, Roels H, Bogaert A, Barbier C: Aprindine-induced liver injury. Acta Gastroenterol Belg 15:236–243, 1977.Google Scholar
  435. 435.
    Boura ALA, Green AF: The actions of bretylium: adrenergic neurone blocking and other effects. Br J Pharmacol 14:536–548, 1959.Google Scholar
  436. 436.
    Boura ALA, Green AF: Adrenergic neurone blocking agents. Ann Rev Pharmacol 5:183–212, 1965.Google Scholar
  437. 437.
    Heissenbuttel RH, Bigger JT Jr: Bretylium tosylate: a newly available antiarrhythmic drug for ventricular arrhythmias. Ann Intern Med 91:229–238, 1979.PubMedGoogle Scholar
  438. 438.
    Bacaner MG: Bretylium tosylate for suppression of induced ventricular fibrillation. Am J Cardiol 17:528–534, 1966.PubMedGoogle Scholar
  439. 439.
    Bigger JR Jr, Jaffe C: The effect of bretylium tosylate on the electrophysiological properties of ventricular muscle and Purkinje fibers. Am J Cardiol 27:82–90, 1971.PubMedGoogle Scholar
  440. 440.
    Wit AL, Steiner C, Damato AN: Electrophysiologic effects of bretylium tosylate on single fibers of the canine specialized conducting system and ventricle. J Pharmacol Exp Ther 173:344–356, 1970.PubMedGoogle Scholar
  441. 441.
    Namm DH, Wang CM, El-Sayad S, Copp FC, Maxwell R A: Effect of bretylium on rat cardiac muscle: the electrophysiologic effects and its uptake and binding in normal and immunosympathectomized rat hearts. J Pharmacol Exp Ther 193:194–208, 1975.PubMedGoogle Scholar
  442. 442.
    Papp JG, Vaughan Williams EM: The effect of bretylium on intracellular cardiac action potentials in relation to itsantiarrhythmic and local anesthetic activity. Br J Pharmacol 37:380, 1969.PubMedGoogle Scholar
  443. 443.
    Cardinal R, Sasyniuk BI: Electrophysiological effects of bretylium tosylate on subendocardial Purkinje fibers from infarcted canine hearts. J Pharmacol Exp Ther 204:159–174, 1978.PubMedGoogle Scholar
  444. 444.
    Glassman RD, Wit AL: Electrophysiological effects of bretylium tosylate. In: Bretylium Tosylate: Current Scientific and Clinical Experience. Excerpta Medica, Amsterdam, 1979.Google Scholar
  445. 445.
    Touboul P, Porte J, Huerta F, Delahaye JP: Etude des propriétés électrophysiologiques du tosylate de bretylium chez l’homme. Arch Mal Coeur 69:503–511, 1976.PubMedGoogle Scholar
  446. 446.
    Waxman MB, Wallace AG: Electrophysiologic effects of bretylium tosylate on the heart. J Pharmacol Exp Ther 183: 264–274, 1972.PubMedGoogle Scholar
  447. 447.
    Allen JD, Pantridge JF, Shanks RG: Effects of lignocaine, propranolol and bretylium on ventricular fibrillation threshold. Am J Cardiol 28:555–562, 1971.PubMedGoogle Scholar
  448. 448.
    Sanna G, Arcidiacono R: Chemical ventricular defibrillation of the human heart with bretylium tosylate. Am J Cardiol 32:982–987, 1973.PubMedGoogle Scholar
  449. 449.
    Kuntzman R, Tsai I, Chang R, Conney AH: Disposition of bretylium in man and rat. Clin Pharmacol Ther 11:829–837, 1970.PubMedGoogle Scholar
  450. 450.
    Bernstein JG, Koch-Weser J: Effectiveness of bretylium tosylate against refractory ventricular arrhythmias. Circulation 45:1024–1034, 1972.PubMedGoogle Scholar
  451. 451.
    Singh BN, Vaughan Williams EM: The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol 39: 657–667, 1970.PubMedGoogle Scholar
  452. 452.
    Charlier R, Deltour G, Tondeur R, Binon F: Recherches dans la série des benzofurannes. VII. Etude pharmacologique préliminaire du butyl-2-(duodo-3’, 5’ β-N-diethylaminoethexy-4’benzoyl)-3 benzofurane. Arch Int Pharmacodyn Ther 139:255–264, 1962.PubMedGoogle Scholar
  453. 453.
    Charlier R, Delaunois G, Bauthier J, Deltour G: Dans la série des benzofurannes. XL. Propriétés antiarrhythmiques de amiodarone. Cardiologia 54:82–90, 1969.Google Scholar
  454. 454.
    Rosenbaum MB, Chiale PA, Halpern MS, Nau GJ, Przybylski J, Levi RJ, Lazzari JO, Elizari MV: Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol 38:934–944, 1976.PubMedGoogle Scholar
  455. 455.
    Goupil N, Lenfant J: The effects of amiodarone on the sinus node activity of the rabbit heart. Eur J Pharmacol 39:23–31, 1976.PubMedGoogle Scholar
  456. 456.
    Broekhuysen J, Deltour G, Gluslain M: Some biochemical effects of amiodarone. Arzneimittelforsch 19:1850–1853, 1969.Google Scholar
  457. 457.
    Grand A: Myxoedème à l’amiodarone. Coeur Med Intern 14:163–167, 1975.PubMedGoogle Scholar
  458. 458.
    Burger A, Dinichert D, Nicod P, Tenny M, Lemarchand-Beraud T, Vallotton MB: Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin and thyrotropin. J Clin Invest 58:255–259, 1976.PubMedGoogle Scholar
  459. 459.
    Baillet J: Amiodarone et dysthyroide: colloque sur l’amiodarone. Documentation Labaz(Paris), 1977, pp 130–135.Google Scholar
  460. 460.
    Jonckheer MH, Blockx P, Kaivers R, Wyffels G: Hyperthyroidism as a possible complication of the treatment of ischemic heart disease with amiodarone. Acta Cardiol 28:192–200, 1973.PubMedGoogle Scholar
  461. 461.
    Charlier R, Deltour G, Baudine A, Chaillet F: Pharmacology of amiodarone an antianginal drug with a new biological profile. Arzneimittelforsch 11:1408–1417, 1968.Google Scholar
  462. 462.
    Charlier R: Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors. Br J Pharmacol 39:668–674, 1970.PubMedGoogle Scholar
  463. 463.
    Bacq AM, Blakeley AGH, Summers RJ: The effects of amiodarone, an α and β receptor antagonist, on adrenergic transmission in the cat and spleen. Biochem Pharmacol 25:1195–1199, 1976.PubMedGoogle Scholar
  464. 464.
    Sicart M, Besse P, Choussat A, Bricaud H: Action hémodynamique de l’amiodarone intraveineuse chez l’homme. Arch Mal Coeur 70:219–227, 1977.PubMedGoogle Scholar
  465. 465.
    Cabasson J, Puech P, Mellet JM, Guimond C, Bachy C, Sassine A: Analyse des effets électrophysiologiques de l’amiodarone par l’enregistrement simultane des potentiels d’action monophasiques et du faisceau de His. Arch Mal Coeur 69:691–699, 1976.PubMedGoogle Scholar
  466. 466.
    Touboul P, Huerta F, Porte J, Delahaye JP: Bases électrophysiologiques de Taction antiarrhythmique de l’amiodarone chez l’homme. Arch Mal Coeur 69:845–853, 1976.PubMedGoogle Scholar
  467. 467.
    Coulte R, Fontaine G, Franks R: Etude électrocardiologique des effets de l’amiodarone sur la conduction introcardiaque chez l’homme. Ann Cardiol Angiol (Paris) 18: 543–548, 1977.Google Scholar
  468. 468.
    Rosenbaum MB, Chiale PA, Ryba D, Elizari MV: Control of tachyarrhythmias associated with Wolff-Parkinson-White syndrome by amiodarone hydrochloride. Am J Cardiol 34:215–222, 1974.PubMedGoogle Scholar
  469. 469.
    Wellens HJJ, Lie KI, Bar FW, Wesdorp JC, Dohmen HJ, Duren DR, Durrer D: Effect of amiodarone in the Wolf-Parkinson-White syndrome. Am J Cardiol 38:189–194, 1976.PubMedGoogle Scholar
  470. 470.
    Rowland E, Krikler DM: Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias. Br Heart J 44:82–90, 1980.PubMedGoogle Scholar
  471. 471.
    Rasmussen V, Berning J: Effect of amiodarone in the Wolff-Parkinson-White syndrome. Acta Med Scand 205:31–37, 1979.PubMedGoogle Scholar
  472. 472.
    Petta JM, Zaccheo VJ: Comparative profile of L 3428 and other antianginal agents on cardiac hemodynamics. J Pharmacol Exp Ther 176:328–338, 1971.PubMedGoogle Scholar
  473. 473.
    Cote P, Bourassa MG, Delaye J, Janin A, Froment R, David P: Effects of amiodarone on cardiac and coronary hemodynamics and on myocardial metabolism in patients with coronary artery disease. Circulation 59:1165–1172, 1979.PubMedGoogle Scholar
  474. 474.
    Barzin J, Freson A: Essais cliniques de l’amiodarone dans les affections coronariennes. Brux Med 49:105, 1969.PubMedGoogle Scholar
  475. 475.
    Kannan R, Ikeda N, Prasad K, Kay I, Ooktens M, Singh B: Plasma kinetics and myocardial disposition of intravenous amiodarone relative to its electrophysiological effects in rabbits and dogs. Circulation 64 (Suppl IV):IV-69, 1981.Google Scholar
  476. 476.
    Haffajee C, Lesko L, Canada A, Alpert JS: Clinical pharmcokinetics of amiodarone. Circulation 64 (Suppl IV):IV-263, 1981.Google Scholar
  477. 477.
    Harris L, McKenna WJ, Rowland E, Storey GCA, Krikler DM, Holt DW: Plasma amiodarone and desethyl amiodarone levels in chronic oral therapy. Circulation 64(Suppl IV):IV-263, 1981.Google Scholar
  478. 478.
    Pritchard DA, Singh BN, Hurley PJ: Effects of amiodarone on thyroid function in patients with ischemic heart disease. Br Heart J 37:856–860, 1975.PubMedGoogle Scholar
  479. 479.
    Bockhardt H, Drenckhahn D, Lullman-Rauch R: Amiodarone-induced lipidosis-like alterations in ocular tissues of rats. Albrecht Von Graefes Arch Klin Exp Ophthamol 207:91–96, 1978.Google Scholar
  480. 480.
    Sobol SM, Rakita L: Pneumonitis and pulmonary fibrosis associated with amiodarone treatment: a possible complication of new antiarrhythmic drug. Circulation 65:819–824, 1982.PubMedGoogle Scholar
  481. 481.
    Kaverina NV, Senova ZP: Ethmozin - a new preparation for treating cardiac rhythm disorders. Proc First US- USSR Symp on Sudden Death, Yalta, Oct 3–5, 1977. US Dept of HEW, PHS, NTH, DHEW Publ No 78:1470, 1978.Google Scholar
  482. 482.
    Morganroth J, Pearlman AS, Dunkman WB, Horowitz LN, Josephson ME, Michelson EL: Ethmozin: a new antiarrhythmic agent developed in the USSR. Efficacy and tolerance. Am Heart J 98:621–628, 1979.PubMedGoogle Scholar
  483. 483.
    Podrid PJ, Lyakishev A, Lown B, Mazur N: Ethmozin, a new antiarrhythmic drug for suppressing ventricular premature complexes. Circulation 61:450–457, 1980.PubMedGoogle Scholar
  484. 484.
    Danilo P Jr, Langan WB, Rosen MR, Hoffman BF: Effects of the phenothiazine analog EN 313 on ventricular arrhythmias in dogs. Eur J Pharmacol 45:127–139, 1977.PubMedGoogle Scholar
  485. 485.
    Ruffy R, Rozenshtraukh LV, Elharrar V, Zipes DP: Electrophysiological effects of ethmozine on canine myocardium. Cardiovasc Res 13:354–363, 1979.PubMedGoogle Scholar
  486. 486.
    Dangman KH, Hoffman BF: Effects of ethmozin on automatic and triggered impulse initiation in canine cardiac Purkinje fibers. J Pharmacol Exp Ther (in press).Google Scholar
  487. 487.
    Hewett K, Gessman L, Rosen MR: The effects of procaine amide, quinidine and ethmozin on ouabain-induced delayed afterdepolarizations. Eur J Pharmacol (submitted).Google Scholar
  488. 488.
    Morganroth J, Michelson EL, Klitchen JG, Dreifus LS: Ethmozin: electrophysiologic effects in man. Circulation 64(IV):263, 1981.Google Scholar
  489. 489.
    Singh SN, DiBianco R, Fletcher RD, Johnson WL, Ginsberg R: Ethmozin shown effective in reducing chronic high frequency: results of a prospective controlled trial. Am J Cardiol 49:1015, 1982.Google Scholar
  490. 490.
    Zaslovskaya RM, Skorobogatskya IF, Kolbanovskaya EY: Ethmozin therapy of patients with rhythm disturbances in heart activity. Sov Med 5:50, 1969.Google Scholar
  491. 491.
    Golochevskaya V A, Bokeriya OA: Application of ethmozin in patients with heart rhythm disturbances. In: Sivkov II, Kukes VG (eds) Questions of Pharmcotherapy of Some Cardiovascular Disease. Moscow, 1971, pp 5–7.Google Scholar
  492. 492.
    Wit AL, Rosen MR, Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias. II. Relationship of normal and abnormal electrical activity of cardiac fibers to the genesis of arrhythmias. A. Automaticity. Am Heart J 88:515–524, 1974.PubMedGoogle Scholar
  493. 493.
    Wit AL, Rosen MR, Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias. II. Relationship of normal and abnormal electrical activity of cardiac fibers to the genesis of arrhythmias B. Reentry. Am Heart J 88:664–670, 1974.PubMedGoogle Scholar
  494. 494.
    Hoffman BF, Rosen MR: Cellular mechanisms for cardiac arrhythmias. Circ Res 49:1–15, 1981.PubMedGoogle Scholar
  495. 495.
    Vassalle M: Analysis of cardiac pacemaker potential using a ‘voltage clamp’ technique. Am J Physiol 210:1335–1341, 1966.PubMedGoogle Scholar
  496. 496.
    Noma A, Irisawa H: A time and voltage-dependent potassium current in the rabbit sino-atrial node cell. Pflugers Arch 336:251–258, 1976.Google Scholar
  497. 497.
    Vassalle M: The relationship among cardiac pacemakers. Overdrive suppression. Circ Res 41:269–277, 1977.PubMedGoogle Scholar
  498. 498.
    Hoffman BF, Cranefield PF: Electrophysiology of the Heart. McGraw Hill, New York, 1960.Google Scholar
  499. 499.
    Surawicz B, Imanish S: Automatic activity in depolarized guinea pig ventricular myocardium: characteristics and mechanisms. Circ Res 39:751–759, 1976.PubMedGoogle Scholar
  500. 500.
    Brown HF, Clark A, Noble SJ: Pacemaker current in frog atrium. Nature 235:30–31, 1972.Google Scholar
  501. 501.
    Cranefield PF: The Slow Response and Cardiac Arrhythmias. Futura Press, Mt. Kisco, 1975.Google Scholar
  502. 502.
    Arnsdorf MF, Mehlman DJ: Observations on the effects of selected antiarrhythmic drugs on mammalian cardiac Purkinje fibers with two levels of steady-state potential: influences of lidocaine, phenytoin, propranolol, disopyramide and procainamide on repolarization, action potential shape and conduction. J Pharmacol Exp Ther 207:983–991, 1978.PubMedGoogle Scholar
  503. 503.
    Cranefield PF: Action potentials, after potentials and arrhythmias. Circ Res 41:415–423, 1977.PubMedGoogle Scholar
  504. 504.
    Wit AL, Cranefield PF, Gadsby DC: Triggered activity: In: Zipes DP, Bailey JC, Elharrar V (eds) The Slow Inward Current and Cardiac Arrhythmias. Martinus Nijhoff, The Hague, 1980, pp 437–454.Google Scholar
  505. 505.
    Ferrier GR: Digitalis arrhythmias: role of oscillatory after potentials. Prog Cardiovasc Dis 19:459–474, 1977.PubMedGoogle Scholar
  506. 506.
    El-Sherif N, Zeiler R, Gough WB: Effects of catecholamines verapamil and tetrodotoxin on triggered automaticity in canine ischemic Purkinje fibers. Circulation 62 (pt 2): 281, 1980.Google Scholar
  507. 507.
    Wit AL, Cranefield PF: Reentrant excitation as a cause of cardiac arrhythmias. Am J Physiol 235:H1-H17, 1978.PubMedGoogle Scholar
  508. 508.
    Courtney KR: Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA-968. J Pharmacol Exp Ther 195:225–236, 1975.PubMedGoogle Scholar
  509. 509.
    Hille B: Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515, 1977.PubMedGoogle Scholar
  510. 510.
    Strichartz GR: Molecular mechanisms of nerve block by local anesthetics. Anesthesiology 45:421–441, 1976.PubMedGoogle Scholar
  511. 511.
    Wit AL, Rosen MR, Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias II. Relationship of normal and abnormal electrical activity of cardiac fibers to the genesis of arrhythmias. B. Reentry, section II. Am Heart J 88:798–806, 1974.PubMedGoogle Scholar
  512. 512.
    Gadsby D, Cranefield PF: Electrogenic sodium extrusion in cardiac Purkinje fibers. J Gen Physiol 73:819–837, 1979.PubMedGoogle Scholar
  513. 513.
    Trautwein W: Membrane currents in cardiac muscle fibers. Physiol Res 53:793–835, 1973.Google Scholar

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© Martinus Nijhoff Publishers, Boston, The Hague, Dordrecht, Lancaster 1983

Authors and Affiliations

  • Penelope A. Boyden
  • Andrew L. Wit

There are no affiliations available

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