Studies on the calcium antagonistic action of tetrandrine: IV. Effects of tetrandrine on isoproterenol and calcium-mediated positive chronotropic action in isolated rabbit atria

Abstract

In isolated spontaneously beating atria of rabbits, tetrandrine (Tet) and verapamil (Ver) shifted the concentration-rate curves to isoproterenol (Iso) to the right in a non-parallel manner and depressed their maxima. (±)-propranolol behaved as a competitive β-adrenoceptor antagonist.

The pD’₂ values of Tet and Ver were 6.48 ± 0.45 and 4.30 ± 0.18, respectively. Hence the antagonistic effect of Ver was stronger than that of Tet. The pA₂ of propranolol = 7.86 ± 0.21.

Tet and Ver antagonized the positive chronotropic responses to Ca⁺⁺ (3.3 mM) in spontaneously beating rabbit atria.

It is proposed that Tet is a calcium antagonist similar to Ver. Its inhibitory effect on the tachycardia induced by Iso is due to its action in Ca⁺⁺ which may be an essential modulator of the sequence of events linking β-adrenoceptor activation and heart rate response.

Keywords

tetrandrine / calcium antagonist / atrium of rabbit / iproveratril / propranolol / isoproterenol

References

[1] ChaL, et al. . Antiarrhythmic action of tetrandrine and the total alkaloids of sophora flavescens. Acta Pharmacol Sinica, 1981, 2(1): 26-28

[2] FangDC, et al. . Studies on the calcium antagonistic action of tetrandrine: I. Effects of tetrandrine on the isolated guinea pig atrium. Acta Acad Med Wuhan, 1981, 1(2): 46-50

[3] FangDC, et al. . Effects of tetrandrine on cat papillary muscle. Acta Pharmacol Sinica, 1981, 2(3): 163-66

[4] Van RossumJM, et al. . Cumulative dose-response curvess I. Introduction to the technique. Arch Int Pharmacodyn Ther, 1963, 143(1–2): 240-46

[5] MaoYK, et al. . Comparison of potencies of six Beta-adrenoceptive blocking drugs in isolated rabbit atrium and guinea pig trachea. Acta Pharmacol Sinica, 1980, 1(1): 7-12

[6] BlackJW, et al. . Comparison of some properties of pronethalol and propranolol. Br J Pharmacol, 1965, 25(3): 557-65

[7] BrileyM, et al. . Evidence against β-adrenoceptor blocking activity of diltiazem, a drug with calcium antagonist properties. Br J Pharmacol, 1980, 69(4): 669-73

[8] JosephsonIRA, et al. . Local anesthetic blockade of Ca⁺⁺-mediated action potentials in cardiac muscle. Eur J Pharmacol, 1976, 40(2): 201-8

[9] NaylerWG, et al. . Calcium antagonists: Definition and mode of action. Basic Res Cardiol, 1981, 76(1): l-15

[10] JinMW, et al. . Influence of tetrandrine on positive inotropic action of isoproterenol and CaCl₂ and on excitation-contraction coupling in isolated cat papillary muscles. Acta Pharmacol Sinica, 1982, 3(2): 97-101