Specific Bradycardic Agents

  • W. Kobinger
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 89)

Abstract

Alinidine (St 567, N-allyl-clonidine), the prototype of the novel class of drugs discussed in this section, has been classified as an antiarrhythmic agent by Millar and Vaughan Williams (1981a) on the basis of its selective electrophysiological effects upon certain myocardial cells. Unlike other agents discussed in this volume, the therapeutic goal searched for was not primarily to interfere with abnormal heart beats, but simply to reduce the sinus node controlled heart rate. In patients where a decrease in myocardial oxygen consumption is a desired therapeutic measure, this might be achieved by a decrease in heart rate (Sonnenblick and Skelton 1971). The expected benefit of a retardation in heart rate for a patient with rigid narrowing of coronary arteries is even more obvious, if the bradycardia is mainly due to a prolongation of the diastolic period, the time span which allows perfusion of the myocardium.

Keywords

Cardiol Propranolol Dine Halothane Atropine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amsterdam EA, Hughes JL, de Maria AN, Zelis R, Mason DT (1974) Indirect assessment of myocardial oxygen consumption in the evaluation of mechanisms and therapy of angina pectoris. Am J Cardiol 33: 737–743Google Scholar
  2. Arndts D, Forster HJ (1981) New aspects in the metabolism of alinidine in man. Eur J Metab Pharmacokinet 6: 313–315CrossRefGoogle Scholar
  3. Arndts D, Leb G, Förster HJ (1981) Pharmacokinetics and metabolism of C-labelled alinidine in man and dog. Eur J Drug Metabol Pharmacol 6: 225–236CrossRefGoogle Scholar
  4. Auböck, J, Konzett H, Olbrich E (1982) The effect of alinidine (St 567) on emotionally induced tachycardia in man. Eur J Clin Pharmacol 21: 467–471PubMedCrossRefGoogle Scholar
  5. Balakumaran K, Lubsen J, Simoons ML, Jovanovic A, ten Cate FJ, van Es GA, Pie- terse H (1984) Anti-anginal effect of the Clonidine derivative alinidine: a comparison with metoprolol. Eur Heart J 5 [Suppl 1]: 271Google Scholar
  6. Bender F, Gülker H (1982) Ein neues Antiarrhythmicum (AQ-A 39) zur Behandlung von Sinustachykardien. Muench Med Wochenschr 124: 97–98Google Scholar
  7. Benedikter L, Trouvain H, Zimmer A (1980) Pharmacodynamics and pharmacokinetics of a new aryl-alkylamine with negative chronotropic effects in man. In: Riet- brock N, Woodcock BG, Neuhaus G (eds) Methods in clinical Pharmacol, the proceedings of an international symposium held in Frankfurt/M. 6-8 May 1979, Vieweg, Braunschweig, pp 44–45Google Scholar
  8. Bouman LN, Duivenvoorden JJ, Opthof T, Treytel BW (1984) Electrophysiological effects of alinidine on nodal and atrial fibres in the guinea-pig heart. J Pharmacol Exp Ther 229: 551–556PubMedGoogle Scholar
  9. Bouman LN, Jongsma HJ, Opthof T, van Ginneken ACG (1985) Does 4 contribute to pace-making in the rabbit sinoatrial node? J Physiol 358: 51 PGoogle Scholar
  10. Clementy J, Hilaire A (1984) Electrophysiological effects of the bradycardic agent falipamil (AQ-A 39) Eur Heart J 5 [Suppl 1]:287 (abstr)Google Scholar
  11. Dämmgen JW, Gross GJ (1985) AQ-AH 208, a new bradycardic agent, increases coronary collateral blood flow to ischemic myocardium. J Cardiovasc Pharmacol 7: 1048–1054CrossRefGoogle Scholar
  12. Dämmgen J, Kadatz R, Diederen W (1981) Cardiovascular actions of 5,6-dimethoxy- 2– [3[[(a(3,4-dimethoxy)-phenylethyl]methylamino]propyl]phthalimidine (AQ- A 39), a specific bradycardic agent. Arzneim Forsch Drug Res 31: 666–670Google Scholar
  13. Dämmgen JW, Lamping KA, Gross G (1985) Actions of two new bradycardic agents, AQ-AH 208 and UL-FS 49, on ischemic myocardial perfusion and function. J Cardiovasc Pharmacol 7: 71–79PubMedCrossRefGoogle Scholar
  14. Dennis PD, Vaughan Williams EM (1986) Further studies of alinidine induced bradycardia in the presence of caesium. Cardiovasc Res 20: 375–378PubMedCrossRefGoogle Scholar
  15. Di Francesco D (1985) The cardiac hyperpolarizing-activated current, /f, origins and developments. Prog Biophys Mol Biol 46: 163–183CrossRefGoogle Scholar
  16. Fitzal S, Zimpfer M (1982) Cardiovascular effects of iV-allyl-clonidine (St 567, alinidine): a substance with specific bradycardic action during neuroleptanesthesia in humans. Int J Clin Pharmacol Ther Toxicol 20: 404–407PubMedGoogle Scholar
  17. Gross GJ, Dämmgen JW (1986) Beneficial effects of two specific bradycardic agents AQ-A 39 (falipamil) and AQ-AH 208 on reversible myocardial reperfusion damage in anesthetized dogs. J Pharmacol Exp Ther 238: 422–428PubMedGoogle Scholar
  18. Gross GJ, Warltier DC, Dämmgen JW (1985) Effects of AQ-AH 208, a new specific bradycardic agent on myocardial ischemia-reperfusion injury in anesthetized dogs. J Cardiovasc Pharmacol 7: 929–936PubMedCrossRefGoogle Scholar
  19. Gruber R, Lumper G, Zilberszac A, Heistracher P (1983) Effects of 1,3,4,5-tetrahydro- 7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)-ethyl]methylimino]propyl]-2H-3- benzazepin-2-on-hydrochloride (UL-FS 49 CI) on the action potential of the guinea-pig heart. Naunyn Schmiedebergs Arch Pharmacol 324:R 32Google Scholar
  20. Gülker H, Holtvogt J, Specker E, Thale J, Heuer H, Bender F (1986) Elektrophysiolo- gische und haemodynamische Wirkungen der neuen bradykardisierenden Substanz AQ-A 39. Z Kardiol 75: 47–51PubMedGoogle Scholar
  21. Guth BD, Heusch G, Ross J (1987) Elimination of exercise-induced regional myocardial dysfunction by a bradycardic agent in dogs with chronic coronary stenosis. Circulation 75: 661–669PubMedCrossRefGoogle Scholar
  22. Haberl R, Steinbeck G (1985) Chronotropic action of alinidine on the isolated sinus node of the rabbit heart. Eur Heart J 6: 730–736PubMedGoogle Scholar
  23. Hageman GR, Neely BH, Urthaler F, James TH (1985) Negative chronotropic and parasympatholytic effects of alinidine on canine sinus node and AV junction. Am J Physiol 248: H324 - H330PubMedGoogle Scholar
  24. Harron DWG, Ridell JG, Shanks RG (1981) Alinidine reduces heart-rate without blockade of beta-adrenoceptors. Lancet i: 351–353Google Scholar
  25. Harron DWG, Shanks RG (1985) Pharmacology, clinical pharmacology and potential therapeutic uses of the specific bradycardic agent alinidine. Eur Heart J 6: 722–729PubMedGoogle Scholar
  26. Harron DWG Allen J, Wilson R, Shanks RG (1982 a) Effect of alinidine on experimental cardial arrhythmias. J Cardiovasc Pharmacol 4: 221–225Google Scholar
  27. Harron DWG, Arndts D, Shanks RG (1982 b) Alinidine pharmacokinetics following acute and chronic dosing. Br J Clin Pharmacol 13: 821–827Google Scholar
  28. Harron DWG, Jady K, Riddell JG, Shanks RG (1982 c) Effects of alinidine, a novel bradycardic agents, on heart rate and blood pressure in man. J Cardiovasc Pharmacol 4: 213–220Google Scholar
  29. Harron DWG, Arndts D, Finch M, Shanks RG (1983) An assessment of the contribution of Clonidine metabolised from alinidine to the cardiovasular effects of alinidine. Br J Clin Pharmacol 16: 451–455PubMedGoogle Scholar
  30. Harron DWG, Brezina, M, Lillie C, Kobinger W (1985) Antifibrillatory properties of alinidine after coronary artery occlusion in rats. Eur J Pharmacol 110: 301–308PubMedCrossRefGoogle Scholar
  31. Hellner KA, Gauri KK (1982) Über Akkomodationsphosphene. Fortschr Ophthalmol 79: 169–170PubMedGoogle Scholar
  32. Herzog H, Simon H (1983) Untersuchungen zur Frequenzsenkung bei Sinustachykar- die und tachykardem Vorhofflimmern unterschiedlicher Ätiologie mit einer neuen bradykardisierenden Substanz (AQ-A 39). Herz/Kreislauf 7: 354–357Google Scholar
  33. Hilaire J, Broustet JP, Colle JP, Theron M (1983) Cardiovascular effects of AQ-A 39 in healthy volunteers. Br J Clin Pharmacol 16: 627–631PubMedGoogle Scholar
  34. Hohnloser SJ, Weirich J, Homburger H, Antoni H (1982) Electrophysiological studies on effects of AQ-A 39 in the isolated guinea-pig heart and myocardial preparations. Arzneim Forsch/Drug Res 32: 730–734Google Scholar
  35. Jähnel C, Nawrath M (1985) Interactions of alinidine and acetylcholine in guinea pig atria. Naunyn Schmiedebergs Arch Pharmacol 329: R54Google Scholar
  36. Jaski BE, Serruys PW (1985) Anion-channel blockade with alinidine: a specific bradycardic drug for coronary heart disease without negative inotropic activity? Am J Cardiol 56: 270–275PubMedCrossRefGoogle Scholar
  37. Jost S, Schulz W, Kober G (1985) Wirkung des neuen Kalziumantagonisten 5,6-Dime- thoxy-2-[3[[of-(3,4-dimethoxy)-phenylethyl]methylamino]propyl]-phthalimidin-hy- drochlorid (AQ-A 39 Cl) auf Hämodynamik und Ischämieparameter in Belastungs-EKG von Patienten mit koronarer Herzkrankheit. Arzneim Forsch/Drug Res 35: 1279–1282Google Scholar
  38. Kasper W, Meinertz T, Treese N, Kersting F, Pop T, Jähnchen E (1981) Clinical electrophysiological properties of N-allyl-clonidine (St 567) in man. J Cardiovasc Pharmacol 3: 39 - 47PubMedCrossRefGoogle Scholar
  39. Kawada M, Satoh K, Taira N (1984 a) Selectivity of alinidine, a bradycardic agent, for SA nodal automaticity versus other cardiac activities in isolated, blood-perfused dog-heart preparations. Arch Int Pharmacodyn Ther 272: 88–102Google Scholar
  40. Kawada M, Satoh K, Taira N (1984 b) Analyses of the cardiac action of the bradycardic agent, AQ-A 39, by use of isolated, blood perfused dog-heart preparations. J Pharmacol Exp Ther 228: 484–490Google Scholar
  41. Khosropour R, Zimpfer M, Lackner F (1983) Slow channel calcium blockade to antagonize the chronotropic effects of isoproterenol. Anesthesiology 59: A43Google Scholar
  42. Kobinger W (1978) Central a-adrenergic systems as targets for hypotensive drugs. Rev. Physiol Biochem Pharmacol 81: 39–100PubMedCrossRefGoogle Scholar
  43. Kobinger W (1985) Specific bradycardic agents, a new approach to therapy in angina pectoris? Prog Pharmacol 5 /4: 89–100Google Scholar
  44. Kobinger W (1986) Drugs as tools in research on adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol 332: 113–123PubMedCrossRefGoogle Scholar
  45. Kobinger W, Lillie C (1987) Specific bradycardic agents - a novel pharmacological class? Eur Heart J 8 (Suppl L): 7–15Google Scholar
  46. Kobinger W, Lillie C (1984 a) Alinidine. In: Scriabine A (ed) Cardiovascular drugs. Raven, New York, pp 193–210 (New drugs annual, vol 2)Google Scholar
  47. Kobinger W, Lillie C (1984b) Cardiovascular characterization of UL-FS 49, 1,3,4,5- tetrahydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)-ethyl]methylimino]- propyl]-2H-3-benzazepin-2-on-hydrochloride, a new “specific bradycardic agent”. Eur J Pharmacol 104: 9–18PubMedCrossRefGoogle Scholar
  48. Kobinger W, Lillie C (1987) Specific bradycardic agents - a novel pharmacological class? Eur Heart J 8 (Suppl L): 7–15PubMedGoogle Scholar
  49. Kobinger W, Lillie C, Pichler L (1979 a) N-Allyl-derivative of Clonidine, a substance with specific bradycardic action at a cardiac site. Naunyn Schmiedebergs Arch Pharmacol 306: 255–262Google Scholar
  50. Kobinger W, Lillie C, Pichler L (1979b) Cardiovascular actions of iV-allyl-clonidine (St 567), a substance with specific bradycardic action. Eur J Pharmacol 58: 141–150PubMedCrossRefGoogle Scholar
  51. Krähenmann R, Heistracher P (1980) Electrophysiological studies of the effects of 5,6-dimethoxy-2-[3-[[a-(3,4-dimethoxy)phenylethyl]methylamino]propyl]phthali- midine (AQ-A 39) in isolated cardiac muscle. Naunyn Schmiedebergs Arch Pharmacol 311: R36Google Scholar
  52. Kray er O (1949) Studies on veratrum alkaloids. VIII. Veratramine, an antagonist to the cardioaccelerator action of epinephrine. J Pharmacol Exp Ther 96: 422–437PubMedGoogle Scholar
  53. Krumpl G, Mayer N, Schneider W, Raberger G (1986 a) Effects of alinidine on exercise-induced regional contractile dysfunction in dogs. Eur J Pharmacol 130: 37–46Google Scholar
  54. Krumpl G, Schneider W, Raberger G (1986b) Can exercise-induced regional contractile dysfunction be prevented by selective bradycardic agents? Naunyn Schmiedebergs Arch Pharmacol 334: 540–543PubMedCrossRefGoogle Scholar
  55. Lillie C, Kobinger W (1983 a) Comparison of the bradycardic effects of alinidine (St 567), AQ-A 39 and verapamil on guinea-pig sinoatrial node superfused with different Ca2+ and NaCl solutions. Eur J Pharmacol 87: 25–33Google Scholar
  56. Lillie C, Kobinger W (1983 b) Actions of alinidine and AQ-A 39 on rate and contractility of guinea pig atria during /?-adrenocoptor stimulation. J Cardiovasc Pharmacol 5: 1048–1051Google Scholar
  57. Lillie C, Kobinger W (1984) Decrease in bradycardic effect of AQ-A 39 and alinidine in guinea-pig sinoatrial node depolarized by high external K+-concentration. Naunyn Schmiedebergs Arch Pharmacol 328: 210–213PubMedCrossRefGoogle Scholar
  58. Lillie C, Kobinger W (1986) Investigations into the bradycardic effects of UL-FS 49 (l,3,4,5-tetrathydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)-ethyl]methyli- mino]propyl]-2-3-benzazepin-2-on hydrochloride) in isolated guinea pig atria. J Cardiovasc Pharmacol 8: 791–797PubMedGoogle Scholar
  59. Lillie C, Kobinger W (1987) Investigations differentiating the mechanism of specific bradycardic agents from that of calcium channel blockers. Naunyn Schmiedebergs Arch Pharmacol 335: 331–333PubMedCrossRefGoogle Scholar
  60. Löllgen H, Just H, Wollschläger H, Kersting F (1981) Hemodynamic actions of alini- dine during exercise in patients with coronary artery disease. Z Kardiol 70: 425–428PubMedGoogle Scholar
  61. Maroko PR, Kjekshus JK, Sobel BE, Watanabe T, Covell JW, Ross J Jr, Braunwald E (1971) Factors influencing infarct size following experimental coronary artery occlusions. Circulation 43: 67–82PubMedGoogle Scholar
  62. Meinertz T, Kasper W, Kersting F, Wiegand U, Jähnchen E, Pop T (1980) Wirkung von Alinidine bei koronarer Herzkrankheit. Z Kardiol 69: 720Google Scholar
  63. Meinertz T, Kasper W, Meier R, Wiegand V, Jähnchen E (1981) Beneficial effects of alinidine in patients with angina. Circulation [Suppl IV] 64: 294Google Scholar
  64. Millar JS, Vaughan Williams EM (1981a) Anion antagonism—a fifth class of antiarrhythmic action? Lancet i: 1291–1293Google Scholar
  65. Millar JS, Vaughan Williams EM (1981b) Pacemaker selectivity: influence on rabbit atria of ionic environment and of alinidine, a possible anion antagonist. Cardio- vasc Res 15: 335–350CrossRefGoogle Scholar
  66. Millar JS, Vaughan Williams EM (1983) Pharmacological mapping of regional effects in the rabbit heart of some new antiarrhythmic drugs. Br J Pharmacol 79: 701–709PubMedGoogle Scholar
  67. Miyamoto J, Kotake H, Mashiba H (1986) Study on bradycardia induced by diltiazem in the rabbit sinoatrial node. Arzneim Forsch/Drug Res 36: 808–810Google Scholar
  68. Neill Wa, Levine HJ, Wagman RJ, Gorlin R (1963) Left ventricular oxygen utilization in intact dogs: effect of systemic hemodynamic factors. Circ Res 12: 163–169Google Scholar
  69. Opthof T, Duivenvoorden JJ, van Ginneken ACG, Jongsma HJ, Bouman L (1986) Electrophysiological effects of alinidine (St 567) on sinoatrial node fibres in the rabbit heart. Cardiovasc Res 20: 727–739PubMedCrossRefGoogle Scholar
  70. Osterrieder W, Pelzer D, Yang Q-F, Trautwein W (1981) The electrophysiological basis of the bradycardic action of AQ-A 39 on the sinoatrial node. Naunyn Schmiedebergs Arch Pharmacol 317: 233–237PubMedCrossRefGoogle Scholar
  71. Pelzer D, Trautwein W, McDonald TF (1982) Calcium channel block and recovery from block in mammalian ventricular muscle treated with organic channel inhibitors. Pflügers Arch 394: 97–105PubMedCrossRefGoogle Scholar
  72. Pichler L (1982) Effect of alinidine (St 567) on sympathetic and vagal activities. Arch Int Pharmacodyn 255: 162–167PubMedGoogle Scholar
  73. Reiterer W (1981) Belastungshämodynamik Koronarkranker nach selektiver Frequenzsenkung (Alinidine). Acta Med Austriaca 8: 182–183Google Scholar
  74. Reiterer W, Stanek B (1980) Einfluß von Alinidine auf die Herzfrequenz unter Ergometerarbeit. Z Kardiol 69: 707Google Scholar
  75. Satoh H, Hashimoto K (1986) Electrophysiological study of alinidine in voltage clamped rabbit sino-atrial node cells. Eur J Pharmacol 121: 211–219PubMedCrossRefGoogle Scholar
  76. Sayen JJ, Sheldon WF, Peirce G, Kuo PT (1958) Polarographic oxygen, the epicardial electrocardiogram and muscle contraction in experimental acute regional ischemia of the left ventricle. Circ Res 6: 779–798PubMedGoogle Scholar
  77. Schamhardt HC, Verdouw PD, Saxena PR (1981) Improvement of perfusion and function of ischemic porcine myocardium after reduction of heart rate by alinidine. J Cardiovasc Pharmacol 3: 728–738PubMedCrossRefGoogle Scholar
  78. Schurmans J, Piessens J, Kesteloot H, de Geest H (1982) Comparative effect of alinidine and propranolol in ischemic heart disease. Eur J Clin Pharmacol 23: 389–396Google Scholar
  79. Shanks RG (1987) The clinical pharmacology of alinidine and its side effects. Eur Heart J 8 (Suppl L): 83–90PubMedGoogle Scholar
  80. Siegl PKS, Wenger HC, Sweet CS (1984) Comparison of cardiovascular responses to the bradycardic drugs, alinidine, AQ-A 39, and mixidine, in the anesthetized dog. J Cardiovasc Pharmacol 6: 565–574PubMedCrossRefGoogle Scholar
  81. Simoons ML (1985) Clinical evaluation of alinidine, a specific sinus node inhibitor. Prog Pharmacol 5[4]101–108Google Scholar
  82. Simoons ML, Balakumaran K (1981) The effects of drugs on the exercise electrocardiogram. Cardiology [Suppl 2] 63: 124–132CrossRefGoogle Scholar
  83. Simoons ML, Hugenholtz PG (1982) Alinidine, a new drug for treatment of sinus tachycardia in myocardial infarction of cardiogenic shock. Am J Cardiol 49: 980CrossRefGoogle Scholar
  84. Simoons ML, Hugenholtz PG (1984) Haemodynamic effects of alinidine, a specific sinus node inhibitor, in patients with unstable angina or myocardial infarction. Eur Heart J 5: 227–232PubMedGoogle Scholar
  85. Simoons ML, Hugenholtz PG (eds) (1987) Heart rate reduction. A reinvented approach to cardiac physiology and therapy. Eur Heart J 8 (Suppl L)Google Scholar
  86. Simoons ML, Tummers J, van Meurs-van Woezik H, van Domburg R (1982) Alinidine, a new agent which lowers heart rate in patients with angina pectoris. Eur Heart J 3: 542–545Google Scholar
  87. Snyders DJ, van Bogaert PP (1985) Mode of action of alinidine, a new bradycardic agent: a voltage-clamp study. J Am Coll Cardiol 5: 494Google Scholar
  88. Snyders DJ, van Bogaert PP (1987) Alinidine modifies the pacemaker current in sheep Purkinje fibers. Pflügers Arch 410: 83–91PubMedCrossRefGoogle Scholar
  89. Sonnenblick EH, Skelton CL (1971) Oxygen consumption of the heart: physiological principles and clinical implications. Mod Concepts Cardiovasc Dis 40: 9–16Google Scholar
  90. Stähle H, Daniel H, Kobinger W, Lillie C, Pichler L (1980) Chemistry, pharmacology and structure-activity relationship with a new type of imidazolines exerting a specific bradycardic action at a cardiac site. J Med Chem 23: 1217–1222PubMedCrossRefGoogle Scholar
  91. Stanek B, Reiterer W, Placheta P, Raberger G (1983) Acute effects of alinidine on heart rate and blood pressure in healthy subjects and patients with hyperkinetic heart syndrome. Eur J Clin Pharmacol 24: 31–34PubMedCrossRefGoogle Scholar
  92. Struyker-Boudier H, Smits J, van Essen H (1981) Haemodynamic effects of alinidine (St 567), a specific bradycardic agent, in the conscious spontaneously hypertensive rat. Naunyn Schmiedebergs Arch Pharmacol 316 [Suppl]: R42CrossRefGoogle Scholar
  93. Takeda K, Akera T, Brody TM (1980) Cardiovascular actions of mixidine fumarate. Eur J Pharmacol 68: 129–137PubMedCrossRefGoogle Scholar
  94. Traunecker W, Walland A (1980) Haemodynamic and electrophysiologic actions of alinidine in the dog. Arch Int Pharmacodyn 244: 58–72PubMedGoogle Scholar
  95. Trautwein W, Pelzer D, McDonald TF, Osterrieder W (1981) AQA 39, a new bradycardic agent which blocks myocardial calcium ( Ca) channels in a frequency and voltage-dependent manner. Naunyn Schmiedebergs Arch Pharmacol 317: 228–232Google Scholar
  96. Trautwein W, Pelzer D, McDonald TF (1983) Interval- and voltage-dependent effects of the calcium channel-blocking agents D 600 and AQA 39 on mammalian ventricular muscle. Circ Res 52 [Suppl I]: 60–68Google Scholar
  97. Tritthart HA, Windisch H, Heuberger S (1981) The effects of the bradycardia-produ- cing compound alinidine on action potentials and tension development in cardiac fibres. Naunyn Schmiedebergs Arch Pharmacol 316: 172–177PubMedCrossRefGoogle Scholar
  98. Urthaler F, Walker AA (1984) Indirect stimulatory action of the calcium channel blocker AQ-A 39. J Pharmacol Exp Ther 230: 336–340PubMedGoogle Scholar
  99. Van Bogaert P-P, Gothals M (1987) Pharmacological influence on the pacemaker current of sheep cardiac Purkinje fibres. A comparison between three different molecules. Eur Heart J 8 (Suppl L): 35–42PubMedGoogle Scholar
  100. Vaughan Williams EM (1984) A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol 24: 129–147PubMedGoogle Scholar
  101. Vaughan Williams EM, Dennis PD, Garnham C (1986) Circadian rhythm of heart rate in the rabbit: prolongation of action potential duration by sustained beta adrenoceptor blockade is not due to associated bradycardia. Cardiovasc Res 20: 528–535PubMedCrossRefGoogle Scholar
  102. Verdouw PD, Saxena PR, Schamhardt HC, van der Hoek TM, Rutterman AM (1980) The effects of alinidine, an 7V-allyl-derivative of Clonidine, on regional myocardial perfusion and performance in the pig with or without artrial pacing. Eur J Pharmacol 64: 209–220PubMedCrossRefGoogle Scholar
  103. Verdouw PD, Gom HPA, Bijleveld RE (1983) Cardiovascular responses to increasing plasma concentrations of AQ-A 39 CI, a new compound with negative chronotropic effects. Arzneim Forsch/Drug Res 33 [l]: 702–706Google Scholar
  104. Warbanow W, Wallukat G, Will-Shahab L (1984) Effects of the bradycardic substance alinidine: (St 567) on cultivated heart myocytes. In: Proc 12 congress of the Ges für Kardiol und Angiol der DDR, Rostock 6-10 November 1984, p 143Google Scholar
  105. Wiegand UW, Kasper W, Meinertz T, Stützle U, Jähnchen E (1982) Pharmacokinetic and pharmacodynamic properties of alinidine in man. J Cardiovasc Pharmacol 4: 59–62PubMedCrossRefGoogle Scholar
  106. Zetler G, Lenschow E, Prenger-Berninghoff W (1968) Die Wirkung von 11 Indol-Alkaloiden auf das Meerschweinchenherz in vivo und in vitro, verglichen mit 2 synthetischen Azepinoindolen, Chinidin und Quindonium. Naunyn Schmiedebergs Arch Pharmakol Exp Pathol 260: 26–49Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • W. Kobinger

There are no affiliations available

Personalised recommendations