Advertisement

How to Test for Antiarrhythmic Drugs

  • Brian F. Hoffman
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 47)

Abstract

I have been asked to consider several related questions. First: When during drug development and testing should electrophysiologic data be acquired? Second, what methods should be used to acquire this data? And, finally, during screening should one employ models of arrhythmias caused by ischemia or models of other sorts?

Keywords

Antiarrhythmic Drug Action Potential Duration Purkinje Fiber Cardiac Sodium Channel Fast Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hondeghem LM, Katzung BG: Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta 472: 373–398, 1977.PubMedGoogle Scholar
  2. 2.
    Courtney KR: Interval-dependent effects of small antiarrhythmic drugs on excitability of guinea pig myocardium. J Mol Cell Cardiol 12: 1273–1273, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Gintant GA, Hoffman BF: Use-dependent block of cardiac sodium channels by quaternary derivatives of lidocaine. Pflugers Arch 400: 121–129, 1984.CrossRefGoogle Scholar
  4. 4.
    Bean BP, Cohen CJ, Tsien RW: Lidocaine binding to resting and inactivated cardiac sodium channels. Biophys J 33: 208, 1981.Google Scholar
  5. 5.
    Trautwein W, Pelzer D, McDonald TF, Osterrieder W: AQA 39, a bradycardic agent which blocks myocardial slow inward channels in a frequency- and voltage-dependent manner. Naunyn-Schmiedeberg’s Arch Pharmacol 317: 228–232, 1981.CrossRefGoogle Scholar
  6. Colatsky TJ: Mechanism 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
  7. 7.
    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 of Na or K Currents? Circ Res 50: 257–272, 1982.PubMedGoogle Scholar
  8. 8.
    DiFrancesco D, Ojeda C; Properties of the pacemaker current if in the sinoatrial node of the rabbit: A comparison with the current iK2in Purkinje fibres. J Physiol 308: 331–351, 1980.PubMedGoogle Scholar
  9. 9.
    Dangman KH, Hoffman BF: Antiarrhythmic effects of ethmozin in cardiac Purkinje fibers: Suppression of automaticity and abolition of triggering. J Pharmacol Exp Ther 227: 578–586, 1983.PubMedGoogle Scholar
  10. 10.
    Ferrier GR, Saunders JH, Méndez C: A cellular mechanism for the generation of ventricular arrhythmias by acetylstrophanthidin. Circ Res 33: 508–515, 1973.PubMedGoogle Scholar
  11. 11.
    Roden DM, Hoffman BF: Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers: relationship to potassium and cycle length. Circulation (in press).Google Scholar
  12. 12.
    Brachmann J, Scherlag BJ, Rosenshtraukh LV, Lazzara R: Bradycardia-dependent triggered activitity: relevance to drug-induced multiform ventricular tachycardia. Circulation 68: 846–856, 1983.PubMedCrossRefGoogle Scholar
  13. Kass RS, Lederer WJ, Tsien RW, Weingart R: Role of calcium ions in transient inward currents and after contractions induced by strophanthidin in cardiac. Purkinje fibres. J Physiol 281: 187–208, 1978.PubMedGoogle Scholar
  14. 14.
    Dangman KH, Hoffman BF: In vivo and in vitro antiarrhythmic and arrhythmogenic effects of N-acetyl procainamide. J Pharmacol Exp Ther 217: 851–862, 1981.PubMedGoogle Scholar
  15. 15.
    El-Sherif N, Gough WB, Zeiller RH, Mehra R: Triggered ventricular rhythms in 1-day-old myocardial infarction in the dog. Circ Res 52: 566–579, 1983.PubMedGoogle Scholar
  16. 16.
    Friedman PL, Stewart JR, Fenoglio JJ Jr, Wit AL: Survival of subendocardial Purkinje fibers after extensive myocardial infarction in dogs. In vitro and in vivo correlations. Circ Res 33: 597–611, 1973.PubMedGoogle Scholar
  17. Sasyniuk BI, Ogilvie RI: Antiarrhythmic drugs: Electrophysiological and pharmacokinetic considerations. Ann Rev Pharmacol Toxicol 15: 131–155, 1975.Google Scholar
  18. 18.
    Eisner DA, Lederer, WJ, Sheu, SS: The role of intracellular sodium activity in the antiarrhythmic action of local anaesthetics in sheep Purkinje fibres. J Physiol 340: 239–257, 1983.PubMedGoogle Scholar
  19. 19.
    Gintant GA, Datyner NB, Cohen IS: Slow inactivation of a tetrodotoxin-sensitive current in canine cardiac Purkinje fibers. Biophys J 45: 509–512, 1984.PubMedCrossRefGoogle Scholar
  20. Attwell D, Cohen I, Eisner D, Ohba M, Ojeda C: The steady state TTX-sensitive (‘window’) sodium current in cardiac Purkinje fibres. Pflugers Arch 379: 137–142, 1979.CrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1985

Authors and Affiliations

  • Brian F. Hoffman

There are no affiliations available

Personalised recommendations