Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1985 Mar;84(3):755–763. doi: 10.1111/j.1476-5381.1985.tb16158.x

A comparison of the effects of bethanidine, meobentine and quinidine on the electrical activity of rat hearts in vivo and in vitro.

B J Northover
PMCID: PMC1987150  PMID: 3986433

Abstract

Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments of the right ventricular free wall of the rat heart during superfusion and electrical stimulation in vitro at 37 degrees C. The sulphates of bethanidine, meobentine or quinidine (4 to 20 microM) applied in vitro caused a prolongation of action potential duration and a delayed and slowed return of electrical excitability following an action potential. Intracardiac electrical stimulation of the urethane-anaesthetized rat heart in situ was used to measure ventricular refractory periods from the electrocardiogram. Intravenous administration of bethanidine, meobentine or quinidine (10 to 20 mg kg-1) caused a prolongation of ventricular refractory periods. Quinidine had a briefer duration of action than either of the other two drugs tested. Urethane-anaesthetized open-chested rats which were subjected to left coronary artery occlusion displayed ventricular tachyarrhythmias in their electrocardiogram. These arrhythmias occurred during the period of occlusion and even more prominently after release of the occlusion. Intravenous administration of bethanidine, meobentine or quinidine (1 to 20 mg kg-1) protected rats against these arrhythmias. The protective effect of quinidine was briefer than that of either of the other two drugs tested.

Full text

PDF
755

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BOURA A. L., GREEN A. F. Adrenergic neurone blockade and other acute effects caused by N-benzyl-N'N"-dimethylguanidine and its ortho-chloro derivative. Br J Pharmacol Chemother. 1963 Feb;20:36–55. doi: 10.1111/j.1476-5381.1963.tb01295.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bacaner M. B., Benditt D. G. Antiarrhythmic, antifibrillatory, and hemodynamic actions of bethanidine sulfate: an orally effective analog of bretylium for suppression of ventricular tachyarrhythmias. Am J Cardiol. 1982 Oct;50(4):728–734. doi: 10.1016/0002-9149(82)91226-7. [DOI] [PubMed] [Google Scholar]
  3. Bacaner M. B., Hoey M. F., Macres M. G. Suppression of ventricular fibrillation and positive inotropic action of bethanidine sulfate, a chemical analog of bretylium tosylate that is well absorbed orally. Am J Cardiol. 1982 Jan;49(1):45–55. doi: 10.1016/0002-9149(82)90276-4. [DOI] [PubMed] [Google Scholar]
  4. Benditt D. G., Benson D. W., Jr, Dunnigan A., Kriett J. M., Pritzker M. R., Bacaner M. B. Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia. Am J Cardiol. 1984 May 1;53(9):1268–1274. doi: 10.1016/0002-9149(84)90077-8. [DOI] [PubMed] [Google Scholar]
  5. Bergey J. L., Nocella K., McCallum J. D. Acute coronary artery occlusion-reperfusion-induced arrhythmias in rats, dogs and pigs: antiarrhythmic evaluation of quinidine, procainamide and lidocaine. Eur J Pharmacol. 1982 Jul 9;81(2):205–216. doi: 10.1016/0014-2999(82)90438-1. [DOI] [PubMed] [Google Scholar]
  6. Clark C., Foreman M. I., Kane K. A., McDonald F. M., Parratt J. R. Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size. J Pharmacol Methods. 1980 Jun;3(4):357–368. doi: 10.1016/0160-5402(80)90077-7. [DOI] [PubMed] [Google Scholar]
  7. Ducouret P. The effect of quinidine on membrane electrical activity in frog auricular fibres studied by current and voltage clamp. Br J Pharmacol. 1976 Jun;57(2):163–184. doi: 10.1111/j.1476-5381.1976.tb07465.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Duncan R. J., Nash C. B. Dose-response effects of quinidine on electrophysiological properties of the heart. Arch Int Pharmacodyn Ther. 1972 Oct;199(2):358–367. [PubMed] [Google Scholar]
  9. Gettes L. S., Reuter H. Slow recovery from inactivation of inward currents in mammalian myocardial fibres. J Physiol. 1974 Aug;240(3):703–724. doi: 10.1113/jphysiol.1974.sp010630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goldberg S., Greenspon A. J., Urban P. L., Muza B., Berger B., Walinsky P., Maroko P. R. Reperfusion arrhythmia: a marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction. Am Heart J. 1983 Jan;105(1):26–32. doi: 10.1016/0002-8703(83)90274-0. [DOI] [PubMed] [Google Scholar]
  11. HALPERN M. H. The dual blood supply of the rat heart. Am J Anat. 1957 Jul;101(1):1–16. doi: 10.1002/aja.1001010102. [DOI] [PubMed] [Google Scholar]
  12. Hoffman B. F., Rosen M. R., Wit A. L. Electrophysiology and pharmacology of cardiac arrhythmias. vii. Cardiac effects of quinidine and procaine amide. B. Am Heart J. 1975 Jul;90(1):117–122. doi: 10.1016/0002-8703(75)90263-x. [DOI] [PubMed] [Google Scholar]
  13. Jaillon P., Schnittger I., Griffin J. C., Winkle R. A. The relationship between the repetitive extrasystole threshold and the ventricular fibrillation threshold in the dog. Non-parallel changes following pharmacological intervention. Circ Res. 1980 May;46(5):599–605. doi: 10.1161/01.res.46.5.599. [DOI] [PubMed] [Google Scholar]
  14. Johnston K. M., MacLeod B. A., Walker M. J. Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics. Can J Physiol Pharmacol. 1983 Nov;61(11):1340–1353. doi: 10.1139/y83-193. [DOI] [PubMed] [Google Scholar]
  15. Kane K. A., Parratt J. R., Williams F. M. An investigation into the characteristics of reperfusion-induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents. Br J Pharmacol. 1984 Jun;82(2):349–357. doi: 10.1111/j.1476-5381.1984.tb10769.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klevans L. R., Kelly R. J., Kovacs J. L. Comparison of the antiarrhythmic activity of quinidine and quinine. Arch Int Pharmacodyn Ther. 1977 May;227(1):57–68. [PubMed] [Google Scholar]
  17. Kowey P. R., Verrier R. L., Lown B. The repetitive extrasystole as an index of vulnerability to ventricular fibrillation during myocardial ischemia in the canine heart. Am Heart J. 1983 Dec;106(6):1321–1325. doi: 10.1016/0002-8703(83)90040-6. [DOI] [PubMed] [Google Scholar]
  18. Manning A. S., Hearse D. J. Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol. 1984 Jun;16(6):497–518. doi: 10.1016/s0022-2828(84)80638-0. [DOI] [PubMed] [Google Scholar]
  19. Marshall R. J., Muir A. W., Winslow E. Development of a severe model of early coronary artery ligation-induced dysrhythmias in the anaesthetized rat. Br J Pharmacol. 1981 Aug;73(4):951–959. doi: 10.1111/j.1476-5381.1981.tb08750.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nattel S., Zeng F. D. Frequency-dependent effects of antiarrhythmic drugs on action potential duration and refractoriness of canine cardiac Purkinje fibers. J Pharmacol Exp Ther. 1984 Apr;229(1):283–291. [PubMed] [Google Scholar]
  21. Nawrath H. Action potential, membrane currents and force of contraction in mammalian heart muscle fibers treated with quinidine. J Pharmacol Exp Ther. 1981 Jan;216(1):176–182. [PubMed] [Google Scholar]
  22. Nawrath H., Eckel L. Electrophysiological study of human ventricular heart muscle treated with quinidine: interaction with isoprenaline. J Cardiovasc Pharmacol. 1979 Jul-Aug;1(4):415–425. doi: 10.1097/00005344-197907000-00004. [DOI] [PubMed] [Google Scholar]
  23. Northover B. J. A comparison of the electrophysiological actions of phentolamine with those of some other antiarrhythmic drugs on tissues isolated from the rat heart. Br J Pharmacol. 1983 Sep;80(1):85–93. doi: 10.1111/j.1476-5381.1983.tb11053.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Patterson E., Amalfitano D. J., Lucchesi B. R. Development of ventricular tachyarrhythmias in the conscious canine during the recovery phase of experimental ischemic injury: effect of bethanidine administration. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):470–475. doi: 10.1097/00005344-198405000-00015. [DOI] [PubMed] [Google Scholar]
  25. SELYE H., BAJUSZ E., GRASSO S., MENDELL P. Simple techniques for the surgical occlusion of coronary vessels in the rat. Angiology. 1960 Oct;11:398–407. doi: 10.1177/000331976001100505. [DOI] [PubMed] [Google Scholar]
  26. Schweitzer P., Mark H. Delayed repolarization syndrome. Am J Med. 1983 Sep;75(3):393–401. doi: 10.1016/0002-9343(83)90339-x. [DOI] [PubMed] [Google Scholar]
  27. Timmis G. C., Gangadharan V., Hauser A. M., Ramos R. G., Westveer D. C., Gordon S. Intracoronary streptokinase in clinical practice. Am Heart J. 1982 Oct;104(4 Pt 2):925–938. doi: 10.1016/0002-8703(82)90266-6. [DOI] [PubMed] [Google Scholar]
  28. VAUGHAN WILLIAMS E. M. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records. Br J Pharmacol Chemother. 1958 Sep;13(3):276–287. doi: 10.1111/j.1476-5381.1958.tb00903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WEST T. C., AMORY D. W. Single fiber recording of the effects of quinidine at atrial and pacemaker sites in the isolated right atrium of the rabbit. J Pharmacol Exp Ther. 1960 Oct;130:183–193. [PubMed] [Google Scholar]
  30. Wallace A. G., Cline R. E., Sealy W. C., Young W. G., Jr, Troyer W. G., Jr Electrophysiologic effects of quinidine. Studies using chronically implanted electrodes in awake dogs with and without cardiac denervation. Circ Res. 1966 Nov;19(5):960–969. doi: 10.1161/01.res.19.5.960. [DOI] [PubMed] [Google Scholar]
  31. Wastila W. B., Copp F. C., Walton E., Ellis C. H., Maxwell R. A. Meobentine sulphate (bis[N-4-methoxybenzyl-N'N"-dimethylguanidine]sulphate): a new antidysrhythmic agent. J Pharm Pharmacol. 1981 Sep;33(9):594–596. doi: 10.1111/j.2042-7158.1981.tb13873.x. [DOI] [PubMed] [Google Scholar]
  32. Zimmerman J. M., Patterson E., Pitt B., Lucchesi B. Antidysrhythmic actions of meobentine sulfate. Am Heart J. 1984 Jun;107(6):1117–1124. doi: 10.1016/0002-8703(84)90266-7. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES