Abstract
1 In Langendorff-perfused rabbit hearts, electrical stimulation threshold and ventricular fibrillation threshold (VFT) were measured by applying rectangular impulses of 3 ms duration and increasing current at frequencies of 4 and 20 Hz respectively. 2 Perfusion with lignocaine or one of three new antiarrhythmic drugs, encainide, lorcainide and ORG 6001, produced significant, dose-dependent increases in both thresholds. 3 On a dosage basis, encainide was seven times, lorcainide fourteen times and ORG 6001 twice as potent as lignocaine in raising VFT. 4 In Langendorff-perfused guinea-pig hearts, only lorcainide provided complete protection against ouabain-induced ventricular fibrillation, while 6 of 6, 3 of 6 and 2 of 6 hearts fibrillated in the presence of encainide, lignocaine and ORG 6001 respectively, but with infusion durations significantly higher than control. 5 These results indicate the potential antifibrillatory activity of these new antiarrhythmic agents.
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- Almotrefi A. A., Baker J. B. Investigation of the antifibrillatory activity of some anticonvulsant gamma-aminobutyric acid-transaminase inhibitors in the rabbit isolated heart: comparison with phenytoin and mexiletine. Br J Pharmacol. 1980;71(2):635–639. doi: 10.1111/j.1476-5381.1980.tb10984.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Almotrefi A. A., Baker J. B. The antifibrillatory potency of aprindine, mexiletine, tocainide and lignocaine compared on Langendorff-perfused hearts of rabbits and guinea-pigs. J Pharm Pharmacol. 1980 Nov;32(11):746–750. doi: 10.1111/j.2042-7158.1980.tb13059.x. [DOI] [PubMed] [Google Scholar]
- Baum T., Eckfeld D. K., Shropshire A. T., Rowles G., Varner L. L. Observations on models used for the evaluation of antiarrhythmic drugs. Arch Int Pharmacodyn Ther. 1971 Sep;193(1):149–170. [PubMed] [Google Scholar]
- Byrne J. E., Gomoll A. W., McKinney G. R. Antiarrhythmic properties of MJ 9067 in acute animal models. J Pharmacol Exp Ther. 1977 Jan;200(1):147–154. [PubMed] [Google Scholar]
- Carmeliet E., Janssen P. A., Marsboom R., Van Nueten J. M., Xhonneux R. Antiarrhythmic, electrophysiologic and hemodynamic effects of lorcainide. Arch Int Pharmacodyn Ther. 1978 Jan;231(1):104–130. [PubMed] [Google Scholar]
- Gibson J. K., Somani P., Bassett A. L. Electrophysiologic effects of encainide (MJ 9067) on canine Purkinje fibres. Eur J Pharmacol. 1978 Nov 15;52(2):161–169. doi: 10.1016/0014-2999(78)90202-9. [DOI] [PubMed] [Google Scholar]
- Kesteloot H., Stroobandt R. Clinical experience with lorcainide (R 15 889), a new anti-arrhythmic drug. Arch Int Pharmacodyn Ther. 1977 Dec;230(2):225–234. [PubMed] [Google Scholar]
- Klotz U., Müller-Seydlitz P., Heimburg P. Disposition and antiarrhythmic effect of lorcainide. Int J Clin Pharmacol Biopharm. 1979 Apr;17(4):152–158. [PubMed] [Google Scholar]
- MCEWEN L. M. The effect on the isolated rabbit heart of vagal stimulation and its modification by cocaine, hexamethonium and ouabain. J Physiol. 1956 Mar 28;131(3):678–689. doi: 10.1113/jphysiol.1956.sp005493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshall R. J., Parratt J. R. Antiarrhythmic, haemodynamic and metabolic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride in greyhounds following acute coronary artery ligation. Br J Pharmacol. 1975 Nov;55(3):359–368. doi: 10.1111/j.1476-5381.1975.tb06939.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore E. N., Spear J. F. Ventricular fibrillation threshold; its physiological and pharmacological importance. Arch Intern Med. 1975 Mar;135(3):446–453. doi: 10.1001/archinte.135.3.446. [DOI] [PubMed] [Google Scholar]
- Salako L. A., Williams V., Wittig J. H. Investigations to characterize a new anti-arrhythmic drug, ORG 6001 including a simple test for calcium antagonism. Br J Pharmacol. 1976 Jun;57(2):251–262. doi: 10.1111/j.1476-5381.1976.tb07475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sami M., Mason J. W., Peters F., Harrison D. C. Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent. Am J Cardiol. 1979 Sep;44(3):526–532. doi: 10.1016/0002-9149(79)90407-7. [DOI] [PubMed] [Google Scholar]
- Vargaftig B. B., Sugrue M. F., Buckett W. R., van Riezen H. ORG 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride), a steroidal anti-arrhythmic agent. J Pharm Pharmacol. 1975 Sep;27(9):697–699. doi: 10.1111/j.2042-7158.1975.tb09535.x. [DOI] [PubMed] [Google Scholar]
- Verdouw P. D., Schamhardt H. C., Remme W. J., De Jong J. W. Antiarrhythmic, metabolic and hemodynamic effects of Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) after coronary flow reduction in pigs. J Pharmacol Exp Ther. 1978 Mar;204(3):634–644. [PubMed] [Google Scholar]
- WILLIAMS E. M., SEKIYA A. Prevention of arrhythmias due to cardiac glycosides by block of sympathetic beta receptors. Lancet. 1963 Feb 23;1(7278):420–421. doi: 10.1016/s0140-6736(63)92306-7. [DOI] [PubMed] [Google Scholar]