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Cardiovascular Drugs and Therapy

, Volume 4, Issue 6, pp 1469–1476 | Cite as

Cardiac versus coronary dilator effects of SD-3211, a new nondihydropyridine calcium antagonist, in isolated, blood-perfused dog hearts

  • Fumiya Yoneyama
  • Hiroaki Yamada
  • Keisuke Satoh
  • Norio Taira
Experimental Pharmacology

Summary

Coronary and cardiac effects of SD-3211 were compared in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. SD-3211 was administered intraarterially. In all preparations SD-3211 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate, and in high doses atrial standstill occurred. The dose that produced a 15% decrease in sinus rate was about 5.6 times the dose that doubled coronary blood flow. In AV node preparations, when injected into the artery supplying the AV node, the drug produced an increase in AV conduction time, and in high doses second- or third-degree AV block occurred. The dose that produced a 15% increase in AV conduction time was about 1.6 times the dose that doubled coronary blood flow. In the same preparations the drug slightly increased AV conduction time only at high doses when injected into the artery supplying the His-Purkinjeventricular system. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. The dose that produced a 50% decrease in the force of contraction of the paced papillary muscle was about 50 times the dose that doubled coronary blood flow. The drug was virtually ineffective on ventricular automaticity. In short, in doses that doubled coronary blood flow, SD-3211 depressed only AV nodal conduction. This cardiovascular profile differs from those of diltiazem and verapamil, which do not discriminate between coronary vasculature and the SA and the AV node.

Key Words

coronary dilator negative dromotropic effect mondihydropyridine calcium antagonist SD-3211 

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References

  1. 1.
    Miyawaki N, Furuta T, Yamauchi H, Iso T. The electrophysiological effects of a novel Ca antagonist, SD-3211, in isolated hearts.Jpn J Pharmacol 1988;46:46P.Google Scholar
  2. 2.
    Nishimura K, Miyawaki N, Yamauchi H, Iso T. Tissue selectivity of the novel calcium antagonist sesamodil fumarate in isolated smooth muscles and cardiac muscles.Arzneimitt Forsch (Drug Res) 1990;40:244–248.Google Scholar
  3. 3.
    Nakayama K, Morimoto K, Harada Y, Tanaka Y. Potent and long-lasting calcium antagonistic actions of SD-3211, a novel benzothiazine derivative assessed in isolated cerebral and coronary arteries. In: Hirvonen L, Timisjärvi J, Niiranen S, Leppäluoto J, eds.Proceedings of the International Union of Physiological Sciences XVII (abstracts), 1989:260.Google Scholar
  4. 4.
    Takada T, Nishimura K, Nakata K, et al. The cardiohemodynamic effect of a novel Ca++ antagonist, SD-3211, in the dog.Jpn J Pharmacol 1989;49:212P.Google Scholar
  5. 5.
    Miyawaki N, Matsuno K, Tsukushi Y, et al. The antihypertensive effect of a novel Ca++ antagonist, SD-3211, in rats.Jpn J Pharmacol 1989;49:210P.Google Scholar
  6. 6.
    Taira N. Effects of diltiazem and other calcium-antagonists on cardiac functions and coronary blood flow as assessed in blood-perfused dog-heart preparations. In: Bing RJ, ed.New Drug Therapy with a Calcium Antagonist: Diltiazem Hakone Symposium '78. Amsterdam, Princeton: Excerpta Medica, 1979:91–103.Google Scholar
  7. 7.
    Taira N. Differences in cardiovascular profile among calcium antagonists.Am J Cardiol 1987;59:24B-29B.PubMedGoogle Scholar
  8. 8.
    Kawada M, Satoh K, Taira N. Profile of coronary vasodilator and cardiac actions of bepridil revealed by use of isolated, blood-perfused heart preparations of the dog.J Cardiovasc Pharmacol 1983;5:604–612.PubMedGoogle Scholar
  9. 9.
    Taira N, Kawada M, Satoh K. Cardiac versus coronary vasodilator actions of KB-944, a new calcium antagonist, assessed in isolated, blood-perfused heart preparations of dogs.J Cardiovasc Pharmacol 1983;5:359–356.Google Scholar
  10. 10.
    Hosono M, Taira N. coronary vasodilator versus cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in the dog heart.J Cardiovasc Pharmacol 1987; 9:633–640.PubMedGoogle Scholar
  11. 11.
    Kubota K, Hashimoto K. Selective stimulation of the parasympathetic preganglionic nerve fibres in the excised and blood-perfused SA node preparation of the dog.Naunyn Schmiedebergs Arch Pharmacol 1973;278:135–150.PubMedGoogle Scholar
  12. 12.
    Hashimoto K, Iijima T, Hashimoto K, Taira N. The isolated and cross-circulated AV node preparation of the dog.Tohoku J Exp Med 1972;107:263–275.PubMedGoogle Scholar
  13. 13.
    Endoh M, Hashimoto K. Pharmacological evidence of autonomic nerve activities in canine papillary muscle.Am J Physiol 1970;218:1459–1463.PubMedGoogle Scholar
  14. 14.
    Litchfield JT Jr, Wilcoxon F. A simplified method of evaluating dose-effect experiments.J Pharmacol Exp Ther 1949;96:99–113.Google Scholar
  15. 15.
    Narimatsu A, Taira N. Effects on atrio-ventricular conduction of calcium-antagonistic coronary vasodilators, local anaesthetics and quinidine injected into the posterior and the anterior septal artery of the atrio-ventricular node preparations of the dog.Naunyn Schmiedebergs Arch Pharmacol 1976;294:169–177.PubMedGoogle Scholar
  16. 16.
    Yatani A, Brown AM, Schwartz A. Bepridil block of cardiac calcium and sodium channels.J Pharmacol Exp Ther 1986;237:9–17.PubMedGoogle Scholar
  17. 17.
    Iijima T, Takahashi K, Taira N. Voltage-and use-dependent block of the inward calcium current by MCI-176, a new nondihydropyridine calcium antagonist, in canine ventricular muscles and single ventricular cells of the guinea-pig.Jpn J Pharmacol 1988;46:155–164.PubMedGoogle Scholar
  18. 18.
    Satoh K, Yanagisawa T, Taira N. Effects on atrioventricular conduction and blood flow of enantiomers of verapamil and of tetrodotoxin injected into the posterior and the anterior septal artery of the atrioventricular node preparation of the dog.Naunyn Schmiedebergs Arch Pharmacol 1979;308:89–98.PubMedGoogle Scholar
  19. 19.
    Nawrath H, Blei I, Gegner R, et al. No stereospecific effects of the optical isomers of verapamil and D-600 on the heart. In: Zanchetti A, Krikler DM, eds.Calcium Antagonism in Cardiovascular Therapy. Experience with Verapamil. Amsterdam: Excerpta Medica, 1981:52–63.Google Scholar
  20. 20.
    Nakajima H, Hoshiyama M, Yamashita K, Kiyomoto A. Effect of diltiazem on electrical and mechanical activity of isolated cardiac ventricular muscle of guinea pig.Jpn J Pharmacol 1975;25:383–392.PubMedGoogle Scholar
  21. 21.
    Nakajima H, Hoshiyama M, Yamashita K, Kiyomoto A. Electrical and mechanical responses to diltiazem in potassium depolarized myocardium of the guinea pig.Jpn J Pharmacol 1976;26:571–580.PubMedGoogle Scholar
  22. 22.
    Brown HF. Electrophysiology of the sinoatrial node.Physiol Rev 1982;62:505–530.PubMedGoogle Scholar
  23. 23.
    Maseri A, Crean PA. Clinical experience with calcium antagonists in angina: What we have learned; What we should know. In: Opie LH, ed.Calcium Antagonists and Cardiovascular Disease. New York: Raven Press, 1984:215–219.Google Scholar
  24. 24.
    Hugenholtz PB, Verdouw PD, de Jong JW, Serruys PW. Nifedipine for angina and acute myocardial ischemia. In: Opie LH, ed.Calcium Antagonists and Cardiovascular Disease. New York: Raven Press, 1984:237–255.Google Scholar
  25. 25.
    Furuta T, Miyawaki N, Yamauchi H, Iso T. The coronary vasodilatory effects of SD-3211 in isolated rabbit hearts.Jpn J Pharmacol 1988;46:189P.Google Scholar
  26. 26.
    Opie LH. Calcium channel antagonists. Part IV. Side effects and contraindications. Drug interactions and combinations.Cardiovasc Drugs Ther 1988;2:177–189.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • Fumiya Yoneyama
    • 1
  • Hiroaki Yamada
    • 1
  • Keisuke Satoh
    • 1
  • Norio Taira
    • 1
  1. 1.Department of PharmacologyTohoku University School of MedicineSendaiJapan

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