Abstract
1. The cardiac actions of amiodarone, a benzofuran derivative used in the treatment of angina pectoris, have been compared with those of (±)-propranolol in anaesthetized dogs.
2. After three successive intravenous injections of propranolol, 0·5 mg/kg, had reduced the heart rate by 25%, a fourth dose had no further negative chronotropic action, but amiodarone, 10 mg/kg intravenously, at this point reduced the heart rate by 23%.
3. Amiodarone, 10 mg/kg intravenously, reduced, but did not abolish, cardiac responses to isoprenaline, 2 μg/kg intravenously. Subsequent successive injections of 10 mg/kg of amiodarone did not further block the responses to isoprenaline, but propranolol, 1 mg/kg intravenously, abolished them.
4. Amiodarone reduced cardiac chronotropic and inotropic responses to glucagon, which were not affected by propranolol.
5. Cardiac output was increased 5 min after amiodarone, 10 mg/kg intravenously, but at 10 min and thereafter it did not differ from control values. Propranolol, 1 mg/kg intravenously, reduced cardiac output by 17% at 5 min, and by 30% after 30 min.
6. From this and other evidence which is discussed, it is concluded that the cardiac actions of amiodarone are not produced by competitive blockade of β-adrenoceptors.
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Selected References
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- Benfey B. G., Greeff K., Heeg E. Evaluation of sympathetic beta-receptor blockade by recording the rate of ventricular pressure rise in cats. Br J Pharmacol Chemother. 1967 May;30(1):23–29. doi: 10.1111/j.1476-5381.1967.tb02109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broeckhuysen J., Deltour G., Ghislain M. Some biochemical effects of amiodarone. Arzneimittelforschung. 1969 Nov;19(11):1850–1853. [PubMed] [Google Scholar]
- Broekhuysen J., Deltour G., Ghislain M., Delbruyère M. Recherches dans la série des benzofurannes. XXIX. Influence de l'aminodarone sur le métabolisme du coeur chez le chien. Biochem Pharmacol. 1967 Nov;16(11):2077–2084. doi: 10.1016/0006-2952(67)90003-2. [DOI] [PubMed] [Google Scholar]
- CHARLIER R., DELTOUR G., TONDEUR R., BINON F. [Studies in the benzofuran series. VII. Preliminary pharmacological study of 2-butyl-3-(3,5-diiodo-4-beta-N-diethylaminoethoxybenzoyl)-benzofuran]. Arch Int Pharmacodyn Ther. 1962 Sep 1;139:255–264. [PubMed] [Google Scholar]
- Charlier R., Baudine A., Chaillet F., Deltour G. Recherches dans la série des benzofurannes. XXV. Effets hémodynamiques de l'amiodarone chez le chien. Acta Cardiol. 1967;22(4):323–349. [PubMed] [Google Scholar]
- Charlier R., Deltour G., Baudine A., Chaillet F. Pharmacology of amiodarone, and anti-anginal drug with a new biological profile. Arzneimittelforschung. 1968 Nov;18(11):1408–1417. [PubMed] [Google Scholar]
- Cockburn F., Hull D., Walton I. The effect of lipolytic hormones and theophylline on heat production in brown adipose tissue in vivo. Br J Pharmacol Chemother. 1967 Nov;31(3):568–577. doi: 10.1111/j.1476-5381.1967.tb00421.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DELTOUR G., BINON F., TONDEUR R., GOLDENBERG C., HENAUX F., SION R., DERAY E., CHARLIER R. [Studies in the benzofuran series. VI. Coronary-dilating activity of alkylated and aminoalkylated derivatives of 3-benzoylbenzofuran]. Arch Int Pharmacodyn Ther. 1962 Sep 1;139:247–254. [PubMed] [Google Scholar]
- GOODYER A. V., HUVOS A., ECKHARDT W. F., OSTBERG R. H. Thermal dilution curves in the intact animal. Circ Res. 1959 May;7(3):432–441. doi: 10.1161/01.res.7.3.432. [DOI] [PubMed] [Google Scholar]
- Glick G., Parmley W. W., Wechsler A. S., Sonnenblick E. H. Glucagon. Its enhancement of cardiac performance in the cat and dog and persistence of its inotropic action despite beta-receptor blockade with propranolol. Circ Res. 1968 Jun;22(6):789–799. doi: 10.1161/01.res.22.6.789. [DOI] [PubMed] [Google Scholar]
- Levey G. S., Epstein S. E. Activation of adenyl cyclase by glucagon in cat and human heart. Circ Res. 1969 Feb;24(2):151–156. doi: 10.1161/01.res.24.2.151. [DOI] [PubMed] [Google Scholar]
- Lucchesi B. R. Cardiac actions of glucagon. Circ Res. 1968 Jun;22(6):777–787. doi: 10.1161/01.res.22.6.777. [DOI] [PubMed] [Google Scholar]
- McKenna D. H., Corliss R. J., Sialer S., Zarnstorff W. C., Crumpton C. W., Rowe G. G. Effect of propranolol on systemic and coronary hemodynamics at rest and during simulated exercise. Circ Res. 1966 Sep;19(3):520–527. doi: 10.1161/01.res.19.3.520. [DOI] [PubMed] [Google Scholar]
- Moret P. R., Boufas D., Fournet P. C. Propriétés pharmacologiques d'un nouvel antiangoreaux: l'amiodarone. Schweiz Med Wochenschr. 1969 Jul 26;99(30):1090–1095. [PubMed] [Google Scholar]
- Nakano J., Kusakari T. Effect of beta adrenergic blockade on the cardiovascular dynamics. Am J Physiol. 1966 Apr;210(4):833–837. doi: 10.1152/ajplegacy.1966.210.4.833. [DOI] [PubMed] [Google Scholar]
- Sailer S., Sandhofer F., Bolzano K., Dienstl F., Braunsteiner H. Uber die Wirkung eines beta-Blockers (Propranolol) auf den Umsatz der freien Fettsäuren und den Einbau von freien Fettsäuren in Plasmatriglyceride beim Menschen. Klin Wochenschr. 1967 Jul 1;45(13):670–674. doi: 10.1007/BF01747198. [DOI] [PubMed] [Google Scholar]
- Shanks R. G. The pharmacology of beta sympathetic blockade. Am J Cardiol. 1966 Sep;18(3):308–316. doi: 10.1016/0002-9149(66)90047-6. [DOI] [PubMed] [Google Scholar]
- Singh B. N., Vaughan Williams E. M. The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. 1970 Aug;39(4):657–667. doi: 10.1111/j.1476-5381.1970.tb09891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sowton E., Hamer J. Hemodynamic changes after beta adrenergic blockade. Am J Cardiol. 1966 Sep;18(3):317–320. doi: 10.1016/0002-9149(66)90048-8. [DOI] [PubMed] [Google Scholar]
- Steiner C., Wit A. L., Damato A. N. Effects of glucagon on atrioventricular conduction and ventricular automaticity in dogs. Circ Res. 1969 Feb;24(2):167–177. doi: 10.1161/01.res.24.2.167. [DOI] [PubMed] [Google Scholar]