Wirkungsspektrum der Calciumantagonisten

  • H. Nawrath
Part of the Handbuch der inneren Medizin book series (INNEREN, volume 9 / 1)

Zusammenfassung

Calciumantagonisten sind eine heterogene Gruppe von Substanzen unterschiedlicher Struktur und pharmakologischer Wirkungen. Sie hemmen calciumabhängige Prozesse an verschiedenen biologischen Strukturen durch eine Hemmung der Calciumaufnahme. Wichtigste Vertreter sind Verapamil (Isoptin), Nifedipin (Adalat) und Diltiazem (Dilzem). Der Begriff Calciumantagonismus geht auf Fleckenstein (1967) zurück, der als erster erkannte, daß es sich bei den von Lindner (1960) und von Haas u. Härtfelder (1962) als Koronardilatatoren eingeführten Substanzen Prenylamin (Segontin) bzw. Verapamil nicht, wie zunächst von mehreren Autoren (Haas u. Härtfelder 1962; Melville u. Benfey 1965; Barousch 1967) vermutet, um β-Rezeptoren blockierende Substanzen handelte, sondern um eine neue Gruppe von Pharmaka mit direktem Angriff an der Zellmembran. Entsprechend der Schlüsselrolle von Ca++ bei zahlreichen biologischen Vorgängen (Rasmussen u. Goodman 1977) kann man eine Vielzahl pharmakologischer Wirkungen von Calciumantagonisten vermuten. Möglicherweise aufgrund der Affinität von Calciumantagonisten zu bestimmten Geweben stehen die Wirkungen an der glatten Muskulatur und am Herzen im Vordergrund (Fleckenstein 1977). Calciumabhängige Prozesse in neuronalen Strukturen werden wenig oder in klinisch relevanten Konzentrationen überhaupt nicht beeinflußt (Hagiwara u. Byerly 1981).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Andersson K-E, Ekelund L-G, Johansson BW, Landmark K (1978) Calciumantagonists (Ca-Blockers). Pharmacological, physiological and clinical aspects. Acta Pharmacol Toxicol (Kbh) 43 (I):1–56Google Scholar
  2. Apitz J, Gaissmaier U (1971) Zwischenfall mit tödlichem Ausgang nach intravenöser Injektion von Isoptin. Med Klin 66:751–755PubMedGoogle Scholar
  3. Aronow WS, Lauda D, Plasencia G, Wong R, Karlsberg RP, Ferlinz J (1979) Verapamil in atrial fibrillation and atrial flutter. Clin Pharmacol Ther 26:578–583PubMedGoogle Scholar
  4. Barousch R (1967) Die Behandlung von Herzarrhythmien mit dem Herzsympatholytikum Iproveratril. Wien Klin Wochenschr 79:856–860PubMedGoogle Scholar
  5. Bayer R, Kalusche D, Kaufmann R, Mannhold R (1975) 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 290:81–97PubMedGoogle Scholar
  6. Bayer R, Rodenkirchen R, Kaufmann R, Lee JH, Hennekes R (1977) The effects of nifedipine on contraction and monophasic action potential of isolated cat myocardium. Naunyn Schmiedebergs Arch Pharmacol 301:29–37PubMedGoogle Scholar
  7. Benaim ME (1972) Asystole after Verapamil. Br Med J 1:169–170Google Scholar
  8. Bender F, Kojima N, Reploh HD, Oelmann G (1966) Behandlung tachykarder Rhythmusstörungen des Herzens durch Beta-Rezeptorenblockade des Atrioventrikulargewebes. Med Welt 17:1120–1123Google Scholar
  9. Boothby CB, Garrard CS, Pickering D (1972) Verapamil in cardiac arrhythmias. Br Med J 1:349Google Scholar
  10. Brichard G, Zimmermann PE (1970) Verapamil in cardiac dysrhythmias during anaesthesia. Br J Anaesth 42:1005–1012PubMedGoogle Scholar
  11. Chapelle M, Benaim R, Chiche P, Cabrol CA (1973) L’action du Vérapamil sur les troubles du rythme électrocardiographique. Résultats cliniques et expérimentaux. Thérapie 28:689–701PubMedGoogle Scholar
  12. Chen CM, Gettes LS (1979) Effects of verapamil on rapid Na channel-dependent action potentials of K+-depolarized ventricular fibers. J Pharmacol Exp Ther 209:415–421PubMedGoogle Scholar
  13. Chiba S, Kobayashi M, Furukawa Y (1978) Effects of optical isomers of verapamil on SA nodal pacemaker activity and contractility of the isolated dog heart. Jpn Heart J 19:409–414PubMedGoogle Scholar
  14. Chiou CY, Malagodi MH, Sastry BVR, Posner P (1976) Effects of calcium antagonist, 6-(N,N-diethylamino)hexyl-3,4,5-trimethoxy-benzoate, on digitalis-induced arrhythmias and cardiac contractions. J Pharmacol Exp Ther 198:444–449PubMedGoogle Scholar
  15. Colatsky TJ, Hogan PM (1980) Effects of external calcium, calcium channel-blocking agents, and stimulation frequency on cycle length-dependent changes in canine cardiac action potential duration. Circ Res 46:543–552PubMedGoogle Scholar
  16. Cranefield PF (1975) The conduction of the cardiac impulse. Futura, Mount Kisco NYGoogle Scholar
  17. Cranefield PF, Aronson RS, Wit AL (1974) Effect of verapamil on the normal action potential and on a calcium-dependent slow response of canine cardiac Purkinje fibers. Circ Res 34:204–213PubMedGoogle Scholar
  18. Dangman KH, Hoffman BF (1980) Effects of nifedipine on electrical activity of cardiac cells. Am J Cardiol 46:1059–1067PubMedGoogle Scholar
  19. Danilo P Jr, Hordof AJ, Reder RF, Rosen MR (1980) Effects of verapamil on electrophysiologic properties of blood superfused cardiac Purkinje fibers. J Pharmacol Exp Ther 213:222–227PubMedGoogle Scholar
  20. Dersham GH, Han J (1981) Actions of verapamil on Purkinje fibers from normal and infarcted heart tissues. J Pharmacol Exp Ther 216:261–264PubMedGoogle Scholar
  21. Dominic J, McAllister RG, Kuo C-S, Reddy CP, Surawicz B (1979) Verapamil plasma levels and ventricular rate response in patients with atrial fibrillation and flutter. Clin Pharmacol Ther 26:710–714PubMedGoogle Scholar
  22. Ducouret P (1976) The effect of quinidine on membrane electrical activity in frog auricular fibres studied by current and voltage clamp. Br J Pharmacol 57:163–184PubMedGoogle Scholar
  23. Ehara T, Kaufmann R (1978) The voltage- and time-dependent effects of (-)-verapamil on the slow inward current in isolated cat ventricular myocardium. J Pharmacol Exp Ther 207:49–55PubMedGoogle Scholar
  24. Eichelbaum M, Birkel P, Grube E, Gütgemann V, Somogyi A (1980) Effects of verapamil on P-R-intervals in relation to verapamil plasma levels following single i.v. and oral administration and during chronic treatment. Klin Wochenschr 58:919–925PubMedGoogle Scholar
  25. Einwächter HM, Kern R, Herb J (1979) Effect of lidoflazine on membrane currents and contraction in voltage-clamped frog atrial fibers. Eur J Pharmacol 55:225–232PubMedGoogle Scholar
  26. Elharrar V, Gaum WE, Zipes DP (1977) Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs. Am J Cardiol 39:544–549PubMedGoogle Scholar
  27. Ellrodt G, Chew CYC, Singh BN (1980) Therapeutic implications of slow-channel blockade in cardiocirculatory disorders. Circulation 62:669–679PubMedGoogle Scholar
  28. El-Sherif N, Lazzara R (1979) Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the slow channel. Circulation 60:605–615PubMedGoogle Scholar
  29. Fairhurst AS, Whittaker ML, Ehlert FJ (1980) Interactions of D600 (methoxyverapamil) and local anesthetics with rat brain α-adrenergic and muscarinic receptors. Biochem Pharmacol 29:155–162PubMedGoogle Scholar
  30. Fazzini PF, Marchi F, Pucci P, Ledda F, Mugelli A (1979) Effects of verapamil on ventricular premature beats of acute myocardial infarction. Am Heart J 98:816–818PubMedGoogle Scholar
  31. Filias N (1974) Verapamil-Behandlung bei Herzrhythmusstörungen. Schweiz Rundschau Med (Praxis) 63:66–74Google Scholar
  32. Fleckenstein A (1971) Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. In: Harris P, Opie L (eds) Calcium and the heart. Academic Press, London, pp 135–188Google Scholar
  33. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–166Google Scholar
  34. Fleckenstein A (1981) Pharmacology and electrophysiology of calcium antagonists. In: Calcium antagonism in cardiovascular therapy. Experience with Verapamil. Excerpta Medica, Amsterdam, pp 10–29Google Scholar
  35. Fleckenstein A, Kammermeier H, Döring HJ, Freund HJ (1967) Zum Wirkungsmechanismus neuartiger Koronardilatatoren mit gleichzeitig Sauerstoff-einsparenden Myokard-Effekten, Prenylamin und Iproveratril. Z Kreislaufforsch 56:716–744PubMedGoogle Scholar
  36. Fondacaro JD, Han J, Yoon MS (1978) Effects of verapamil on ventricular rhythm during acute coronary occlusion. Am Heart J 96:81–86PubMedGoogle Scholar
  37. Garvey HL (1969) The mechanism of action of verapamil on the sinus and AV nodes. Eur J Pharmacol 8:159–166PubMedGoogle Scholar
  38. Gotsman MS, Lewis BS, Bakst A, Mitha AS (1972) Verapamil in life-threatening tachyarrhythmias. Afr Med J 46:2017–2019Google Scholar
  39. Grant AO, Katzung BG (1976) The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig. J Pharmacol Exp Ther 196:407–419PubMedGoogle Scholar
  40. Grant AO, Hondeghem LM, Katzung BG (1978) Effects of droperidol on depolarization-induced automaticity, maximum upstroke velocity (̇Vmax) and the kinetics of recovery of ̇Vmax in guinea-pig ventricular myocardium. J Pharmacol Exp Ther 205:193–203Google Scholar
  41. Haap K, Antoni H (1978) Mexiletin — Tierexperimentelle Befunde über die antiarrhythmischen und elektrophysiologischen Effekte am Herzen. Klin Wochenschr 56:169–176Google Scholar
  42. Haas H, Härtfelder G (1962) α-Isopropyl-α-[(N-Methyl-N-homoveratryl)-γ-aminopropyl]-3,4-dimethoxyphenylacetonitril, eine Substanz mit coronargefäßerweiternden Eigenschaften. Arzneim Forsch 12:549–558Google Scholar
  43. Haeusler G (1972) Differential effect of verapamil on excitation-contraction coupling in smooth muscle and on excitation-secretion coupling in adrenergic nerve terminals. J Pharmacol Exp Ther 180:672–682PubMedGoogle Scholar
  44. Hagemeijer F (1977) Verapamil in the management of supraventricular tachyarrhythmias occuring after a recent myocardial infarction. Circulation 57:751–755Google Scholar
  45. Hagiwara S, Byerly L (1981) Calcium channel. Ann Rev Neurosci 4:69–125PubMedGoogle Scholar
  46. Heng MK, Singh BN, Roche AHG, Norris RM, Mercer CJ (1975) Effects of intravenous verapamil on cardiac arrhythmias and on the electrocardiogram. Am Heart J 90:487–498PubMedGoogle Scholar
  47. Henry PD (1980) Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 46:1047–1058PubMedGoogle Scholar
  48. Hescheler J, Pelzer D, Trube G, Trautwein W (1981) Action potentials of isolated ventricular cells following intracellular or extracellular application of D600 and its quaternary derivative. Pflügers Arch [Suppl] 391:R1Google Scholar
  49. Hille B (1977) Local anesthetics: Hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515PubMedGoogle Scholar
  50. Hirata Y, Kodama I, Iwamura N, Shimizu T, Toyama J, Yamada K (1979) Effects of verapamil on canine Purkinje fibres and ventricular muscle fibres with particular reference to the alteration of action potential duration after a sudden increase in driving rate. Cardiovasc Res 13:1–8PubMedGoogle Scholar
  51. Hogan PM, Spitzer KW (1975) Verapamil-induced increases in Purkinje fiber automaticity. Fed Proc 34:375Google Scholar
  52. Hondeghem L, Katzung BG (1980) Test of a model of antiarrhythmic drug action. Effects of quinidine and lidocaine on myocardial conduction. Circulation 61:1217–1224PubMedGoogle Scholar
  53. Hordof AJ, Edie R, Malm JR, Hoffman BF, Rosen MR (1976) Electrophysiologic properties and response to pharmacologic agents of fibers from diseased human atria. Circulation 54:774–779PubMedGoogle Scholar
  54. Huang TF, Peng YJ (1977) Effect of verapamil on experimental arrhythmias. Eur J Pharmacol 42:363–370PubMedGoogle Scholar
  55. Husaini MH, Kvasnicka J, Ryden L, Holmberg S (1973) Action of verapamil on sinus node, atrioventricular and intraventricular conduction. Br Heart J 35:734–737PubMedGoogle Scholar
  56. Iijima T, Taira N (1976) Modification by manganese ions and verapamil of the responses of the atrioventricular node to norepinephrine. Eur J Pharmacol 37:55–62PubMedGoogle Scholar
  57. Ikemoto Y (1977) Reduction by thiopental of the slow-channel-mediated action potential of canine papillary muscle. Pflügers Arch 372:285–286PubMedGoogle Scholar
  58. Imanishi S, McAllister RG, Surawicz B (1978) The effects of verapamil and lidocaine on the automatic depolarizations in guinea-pig ventricular myocardium. J Pharmacol Exp Ther 207:294–303PubMedGoogle Scholar
  59. Kashani IA, Shakibi JG, Siassi B (1980) Effect of verapamil on retrograde ventriculoatrial conduction in children. Jpn Heart J 21:485–490PubMedGoogle Scholar
  60. Kass RS, Tsien RW (1975) Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers. J Gen Physiol 66:169–192PubMedGoogle Scholar
  61. Kaumann AJ, Aramendia P (1968) Prevention of ventricular fibrillation induced by coronary ligation. J Pharmacol Exp Ther 164:326–332PubMedGoogle Scholar
  62. Kaumann AJ, Serur JR (1975) Optical isomers of verapamil on canine heart. Prevention of ventricular fibrillation induced by coronary artery occlusion, impaired atrioventricular conductance and negative inotropic and chronotropic effects. Naunyn Schmiedebergs Arch Pharamcol 291:347–358Google Scholar
  63. Kawai C, Konishi T, Matsuyama E, Okazaki H (1981) Comparative effects of three calcium antagonists, diltiazem, verapamil and nifedipine, on the sinoatrial and atrioventricular nodes. Experimental and clinical studies. Circulation 63:1035–1042PubMedGoogle Scholar
  64. Kecskeméti V, Kelemen K, Knoll J (1978) Effect of verapamil and D600 on cardiac transmembrane potentials. Acta Physiol Acad Sci Hung 51:51–59PubMedGoogle Scholar
  65. Khalsa A, Olsson B, Henriksson B (1979) Effect of oral verapamil on ventricular irregularity in long-standing atrial fibrillation. Acta Med Scand 205:39–47PubMedGoogle Scholar
  66. Klevans LR, Kelly RJ (1978) Effect of autonomic neural blockade on verapamil-induced suppression of the accelerated ventricular escape beat in ouabain-treated dogs. J Pharmacol Exp Ther 206:259–267PubMedGoogle Scholar
  67. Kodama I, Hirata Y, Toyama J, Yamada K (1980) Effects of niludipine (Bay-a-7168) on transmembrane action potentials of rabbit sinus node cells and atrial muscle fibers. J Cardiovasc Pharmacol 2:145–153PubMedGoogle Scholar
  68. Kohlhardt M (1979) Hemmung des Slow-response-Aktionspotentials der Warmblüter-Arbeitsmyokardzelle durch Etafenon. Arzneim-Forsch 29:3–12Google Scholar
  69. Kohlhardt M, Fleckenstein A (1977) Inhibition of the slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol 298:267–272PubMedGoogle Scholar
  70. Kohlhardt M, Haap K (1981) The blockade of Vmax of the atrioventricular action potential produced by the slow channel inhibitors verapamil and nifedipine. Naunyn Schmiedebergs Arch Pharmacol 316:178–185PubMedGoogle Scholar
  71. Kohlhardt M, Mnich Z (1978) Studies on the inhibitory effect of verapamil on the slow inward current in mammalian ventricular myocardium. J Mol Cell Cardiol 10:1037–1052PubMedGoogle Scholar
  72. Kohlhardt M, Wais U (1979) Quantitative differences between the inhibitory action of verapamil and Ni ions on the slow response action potential in mammalian ventricular myocardium. J Mol Cell Cardiol 11:917–921PubMedGoogle Scholar
  73. Kohlhardt M, Bauer B, Krause H, Fleckenstein A (1972) Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors. Pflügers Arch 335:309–322PubMedGoogle Scholar
  74. Kohlhardt M, Haastert HP, Krause H (1973) Evidence of non-specificity of the Ca channel in mammalian myocardial fibre membranes. Pflügers Arch 342:125–136PubMedGoogle Scholar
  75. Kostyuk PG, Krishtal OA, Doroshenko PA (1975) Outward currents in isolated snail neurones. III. Effect of verapamil. Comp Biochem Physiol 51C:269–274Google Scholar
  76. Kostyuk PG, Krishtal OA, Shakkovalov YA (1977) Separation of sodium and calcium current in the somatic membrane of mullusc neurones. J Physiol (Lond) 270:545–568Google Scholar
  77. Krikler D (1974) Verapamil in cardiology. Eur J Cardiol 2:3–10PubMedGoogle Scholar
  78. Krikler D, Spurrell R (1974) Verapamil in the treatment of paroxysmal supraventricular tachycardia. Postgrad Med J 50:447–453PubMedGoogle Scholar
  79. Lathrop DA, Valle R, Gaum WE, Schwartz A, Kaplan S (1981) The effect of diltiazem and nisoldipine on spontaneously active human atrial tissue. J Mol Cell Cardiol 13:111–115PubMedGoogle Scholar
  80. Lewis BS, Mitha AS, Gotsman MS (1976) Immediate haemodynamic effects of verapamil in man. Cardiology 60:366–376Google Scholar
  81. Linden J, Brooker G (1980) The influence of resting membrane potential on the effect of verapamil on atria. J Mol Cell Cardiol 12:325–331PubMedGoogle Scholar
  82. Lindner E (1960) Phenyl-propyl-diphenyl-propyl-amin, eine neue Substanz mit coronargefäßerweiternder Wirkung. Arzneim-Forsch 10:569–573Google Scholar
  83. Ludwig C, Nawrath H (1977) Effects of D-600 and its optical isomers on force of contraction in cat papillary muscles and guinea-pig auricles. Br J Pharmacol 59:411–417PubMedGoogle Scholar
  84. Mangiardi LM, Hariman RJ, McAllister RG Jr, Bhargava V, Surawicz B, Shabetai R (1978) Electrophysiologic and hemodynamic effects of verapamil. Correlation with plasma drug concentrations. Circulation 57:366–372PubMedGoogle Scholar
  85. McAllister RG Jr, Bourne DAW, Dittert LW (1977) The pharmacology of verapamil. I. Elimination kinetics in dogs and correlation of plasma levels with effect on the electrocardiogram. J Pharmacol Exp Ther 202:38–44PubMedGoogle Scholar
  86. McDonald TF, Trautwein W (1978) Membrane currents in cat myocardium: separation of inward and outward components. J Physiol (Lond) 274:193–216Google Scholar
  87. McDonald TF, Pelzer D, Trautwein W (1980) On the mechanism of slow calcium channel block in heart. Pflügers Arch 385:175–179PubMedGoogle Scholar
  88. Matsuyama E, Konishi T, Okazaki H, Matsuda H, Kawai C (1981) Effects of verapamil on accessory pathway properties and induction of circus movement tachycardia in patients with the Wolff-Parkinson-White Syndrome. J Cardiovasc Pharmacol 3:11–24PubMedGoogle Scholar
  89. Melville KI, Benfey BG (1965) Coronary vasodilatory and cardiac adrenergic blocking effects of iproveratril. Can J Physiol Pharmacol 43:339–342PubMedGoogle Scholar
  90. Melville KI, Shister HE, Hug S (1964) Iproveratril: Experimental data on coronary dilatation and antiarrhythmic action. Can Med Assoc J 90:761–770PubMedGoogle Scholar
  91. Milne JR (1972) Verapamil in cardiac arrhythmias. Br Med J 1:348–349Google Scholar
  92. Motomura S, Taira N (1981) Differential effects of organic slow inward current inhibitors, verapamil and nifedipine, on rate of atrioventricular rhythm and supraventricular tachycardia in the canine isolated, blood-perfused AV node preparation. Naunyn Schmiedebergs Arch Pharmacol 315:241–248PubMedGoogle Scholar
  93. Nakajima H, Hoshiyama M, Yamashita K, Kiyomoto A (1975) Effect of diltiazem on electrical and mechanical activity of isolated cardiac ventricular muscle of guinea pig. Jpn J Pharmacol 25:383–392PubMedGoogle Scholar
  94. Narimatsu A, Taira N (1976) Effects on atrio-ventricular conduction of calcium-antagonistic coronary vasodilators, local anaesthetics and quinidine injected into the posterior and the anterior septal artery of the atrio-ventricular node preparation of the dog. Naunyn Schmiedebergs Arch Pharmacol 294:169–177PubMedGoogle Scholar
  95. Nawrath H, TenEick RE, McDonald TF, Trautwein W (1977) On the mechanism underlying the action of D-600 on slow inward current and tension in mammalian myocardium. Circ Res 40:408–414PubMedGoogle Scholar
  96. Nawrath H, Blei I, Gegner R, Ludwig C, Zong X (1981) No stereo specific effects of the optical isomers of verapamil and D600. In: Zanchetti A, Krikler DM (eds) Calcium antagonism in cardiovascular therapy. Experience with verapamil. Excerpta Medica, Amsterdam, pp 52–63Google Scholar
  97. Noma A, Yanagihara K, Irisawa H (1977) Inward current of the rabbit sinoatrial node cell. Pflügers Arch 372:43–51PubMedGoogle Scholar
  98. Okada T (1976) Effect of verapamil on electrical activities of SA node, ventricular muscle and Purkinje fibers in isolated rabbit hearts. Jpn Circ J 40:329–341PubMedGoogle Scholar
  99. Oram S, Catley PF, Livesley B, Kidner PH (1971) An antidysrhythmic agent. Br Med J III:113Google Scholar
  100. Papazoglu NM (1974) Treatment of choice for paroxysmal supraventricular tachycardia. Am J Cardiol 34:743Google Scholar
  101. Payet MD, Schanne OF, Ruiz-Ceretti E (1980 a) Competition for slow channel of Ca2+, Mn2+, verapamil, and D-600 in rat ventricular muscle? J Mol Cell Cardiol 12:635–638PubMedGoogle Scholar
  102. Payet MD, Schanne OF, Ruiz-Ceretti E, Demers J-M (1980 b) Inhibitory activity of blockers of the slow inward current in rat myocardium, a study in steady state and of rate of action. J Mol Cell Cardiol 12:187–200PubMedGoogle Scholar
  103. Posner P, Miller BL, Lambert CR (1975) The effect of verapamil on potassium fluxes in canine cardiac Purkinje fibres. Eur J Pharmacol 34:369–372PubMedGoogle Scholar
  104. Raschack M, Engelmann K (1980) Calcium-antagonistic activity and myocardial ischemia protection by both stereoisomers of verapamil. J Mol Cell Cardiol [Supp. 1] 12:132Google Scholar
  105. Rasmussen H, Goodman DBP (1977) Relationships between calcium and cyclic nucleotides in cell activation. Physiol Rev 57:421–509PubMedGoogle Scholar
  106. Reckless JPD, Gilchrist WSL (1971) An antidysrhythmic agent. Br Med J 4:429PubMedGoogle Scholar
  107. Refsum H (1975) The effect of a calcium-antagonistic drug, nifedipine, on the rat atrial action potential at different calcium levels. Acta Pharmacol Toxicol (Kbh) 37:329–335Google Scholar
  108. Refsum H, Landmark K (1976) The effect of nifedipine on the effective refractory period and excitability of the isolated rat atrium at different calcium levels and frequencies of stimulation. Acta Pharmacol Toxicol (Kbh) 39:353–364Google Scholar
  109. Reuter H (1979) Properties of two inward membrane currents in the heart. Ann Rev Physiol 41:413–424Google Scholar
  110. Reuter H, Scholz H (1977) The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol 264:49–62PubMedGoogle Scholar
  111. Rinkenberger RL, Prystowsky EN, Heger JJ, Troup PJ, Jackman WM, Zipes DP (1980) Effects of intravenous and chronic oral verapamil administration in patients with supraventricular tachyarrhythmias. Circulation 62:996–1010PubMedGoogle Scholar
  112. Rodriguez-Pereira E, Viana AP (1968) The actions of verapamil on experimental arrhythmias. Arzneim-Forsch 18:175–179Google Scholar
  113. Rosen MR, Danilo P (1980) Effects of tetrodotoxin, lidocaine, verapamil, and AHR-2666 on ouabain-induced delayed after depolarizations in canine Purkinje fibers. Circ Res 46:117–124PubMedGoogle Scholar
  114. Rosen MR, Ilvento JP, Gelband H, Merker C (1974) Effects of verapamil on electrophysiologic properties of canine cardiac Purkinje fibers. J Pharmacol Exp Ther 189:414–422PubMedGoogle Scholar
  115. Roy PR, Spurrell RAJ, Sowton E (1974) The effect of verapamil on the cardiac conduction system in man. Postgrad Med J 50:270–275Google Scholar
  116. Sacks H, Kennelly BM (1972) Verapamil in cardiac arrhythmias. Br Med J 2:716PubMedGoogle Scholar
  117. Saikawa T, Nagamato Y, Arita M (1977) Electrophysiologic effects of diltiazem, a new slow channel inhibitor, on canine cardiac fibers. Jpn Heart J 18:235–245PubMedGoogle Scholar
  118. Satoh K, Yanagisawa T, Taira N (1979) Effects on atrioventricular conduction and blood flow of enantiomers of verapamil and of tetrodotoxin injected into the posterior and the anterior septal artery of the atrioventricular node preparation of the dog. Naunyn Schmiedebergs Arch Pharmacol 308:89–98PubMedGoogle Scholar
  119. Satoh K, Yanagisawa T, Taira N (1980) Coronary vasodilator and cardiac effects of optical isomers of verapamil in the dog. J Cardiovasc Pharmacol 2:309–318PubMedGoogle Scholar
  120. Schamroth L, Krikler DM, Garrett C (1972) Immediate effects of intravenous verapamil in cardiac arrhythmias. Br Med J 1:660–662PubMedGoogle Scholar
  121. Schlepper M, Weppner HG, Merle H (1978) Haemodynamic effects of supraventricular tachycardias and their alterations by electrically and verapamil induced termination. Cardiovasc Res 12:28–33PubMedGoogle Scholar
  122. Schmid JR, Hanna C (1967) A comparison of the antiarrhythmic actions of two new synthetic compounds, iproveratril and MJ 1999, with quinidine and pronethalol. J Pharmacol Exp Ther 156:331–338PubMedGoogle Scholar
  123. Seikawa T, Arita M (1980) Effects of verapamil and its optical isomers on repetitive slow responses induced by electrical depolarization in canine ventricular myocardium. Jpn Heart J 21:247–255Google Scholar
  124. Seipel L, Breithardt G, Abendroth RR, Wiebringhaus E (1980) The electrophysiological effects of the Ca-antagonists Gallopamil (D600), Dimeditiapramine (Ro 11–1781) and Verapamil in man. Z Kardiol 69:551–555PubMedGoogle Scholar
  125. Shakibi J, Kashani IA, Mehranpur M, Yazdanyar A (1979) Electrophysiologic effects of verapamil in children. Jpn Heart J 20:789–801PubMedGoogle Scholar
  126. Singh BN, Roche AHG (1977) Effects of intravenous verapamil on hemodynamics in patients with heart disease. Am Heart J 94:593–599PubMedGoogle Scholar
  127. Singh BN, Vaughan Williams EMV (1972) A fourth class of antidysrhythmic action? Effect of verapamil on ouabain toxicity, on atrial and ventricular intracellular potentials, and on other features of cardiac function. Cardiovasc Res 6:109–119PubMedGoogle Scholar
  128. Spear JN, Horowitz LN, Moore EN, McVaugh H (1976) Verapamil-sensitive «slow-response» activity in infarcted human ventricular myocardium. Circulation [Suppl II] 75:53–54Google Scholar
  129. Spurrell RAJ, Krikler DM, Sowton E (1974) Effects of verapamil on electrophysiological properties of anomalous atrioventricular connexion in Wolff-Parkinson-White syndrome. Br Heart J 36:256–264PubMedGoogle Scholar
  130. Sugiyama S, Ozawa T, Suzuki S, Kato T (1980) Effects of verapamil and propranolol on ventricular vulnerability after coronary reperfusion. J Electrocardiol 13:49–54PubMedGoogle Scholar
  131. Talano JV, Singer DH, Loeb HS, TenEick RE, Elson J, Euler DE, Randall WC, Moran JM, Gunnar RM (1976) Intractable ventricular tachyarrhythmia in post-infarction aneurysm: clinical, electrophysiologic and electropharmacologic studies. Clin Res 24:242 AGoogle Scholar
  132. TenEick RE, Singer DH (1973) Effects of perhexiline on the electrophysiologic activity of mammalian heart. Postgrad Med J [April Suppl] 32–42Google Scholar
  133. TenEick RE, Singer DH (1979) Electrophysiological properties of diseased human atrium I. Low diastolic potential and altered cellular response to potassium. Circ Res 44:545–557Google Scholar
  134. Tonkin AM, Aylward PE, Joel SE, Heddle WF (1980) Verapamil in prophylaxis of paroxysmal atrioventricular nodal reentrant tachycardia. 2:473–486Google Scholar
  135. Tse WW, Han J (1975) Effect of manganese chloride and verapamil on automaticity of digitalized Purkinje fibers. Am J Cardiol 36:50–55PubMedGoogle Scholar
  136. Tuganowski W, Kopéc P, Kopyta M, Wȩźowska J (1977) The effect of verapamil and dibutyryl cAMP on the spontaneous activity of the sinus node. Experientia 33:642–643PubMedGoogle Scholar
  137. Urthaler F, James TN (1979) Experimental studies on the pathogenesis of asystole after verapamil in the dog. Am J Cardiol 44:651–656PubMedGoogle Scholar
  138. Vaughan Neil EF, Snell NJC, Bevan G (1972) Hypotension after verapamil. Br Med J 2:529PubMedGoogle Scholar
  139. Vogel S, Crampton R, Sperelakis N (1979) Blockade of myocardial slow channels by bepridil (CERM-1978). J Pharmacol Exp Ther 210:378–385PubMedGoogle Scholar
  140. Vohra J, Hunt D, Stuckey J, Sloman G (1974) Cycle length alternation in supraventricular tachycardia after administration of verapamil. Br Heart J 36:570–576PubMedGoogle Scholar
  141. Watanabe Y, Dreifus LS (1977) Cardiac arrhythmias. Electrophysiologic basis for clinical interpretation. Grune & Stratton, New YorkGoogle Scholar
  142. Wit AL, Cranefield PF (1974) 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 35:413–425PubMedGoogle Scholar
  143. Yamaguchi I, Obayashi K, Mandel WJ (1978) Electrophysiological effects of verapamil. Cardiovasc Res 12:597–608PubMedGoogle Scholar
  144. Zipes DP, Fischer JC (1974) Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventricular conduction in the dog. Circ Res 34:184–192PubMedGoogle Scholar
  145. Zipes DP, Bailey JC, Elharrar V (1980) The slow inward current and cardiac arrhythmias. Martinus Nijhoff, The HagueGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • H. Nawrath

There are no affiliations available

Personalised recommendations