Differences Between Dihydropyridine and Non-Dihydropyridine Calcium Antagonists in Inotropic, Chronotropic, Dromotropic and Vascular Effects: Differences in Underlying Mechanism

  • N. Taira
Part of the Bayer-Symposium book series (BAYER-SYMP, volume 9)


It is generally accepted that nifedipine and nicardipine, dihydropyridine (DHP) calcium antagonists (Ca-antagonists), are less cardiodepressant that verapamil and diltiazem, non-dihydropyridine (non-DHP) Ca-antagonists, in therapeutic doses used in the treatment of angina pectoris and/or hypertension. Such a property of nifedipine is indeed one of its advantages over the two non-DHP Ca-antagonists. However, owing to this property nifedipine tends to produce reflex tachycardia which is thought to be one of its undesirable effects [1]. Among new DHP Ca-antagonists developed recently PY 108–068 [2] and PN 200-110 [3] have been claimed less likely to produce reflex tachycardia. Thus, the question arises whether some of DHP Ca-antagonists produced by some modifications of the chemical structure of nifedipine possess a low separation between the vasodilator and the cardiac effects as do verapamil and diltiazem. The present article first treats this question and afterwards discusses mechanisms underlying a high separation between the vasodilator and the cardiac effects in DHP Ca-antagonists. To settle the first question the article treats seven DHP Ca-antagonists, i.e., nifedipine, nicardipine, nimodipine [4, 5], nisoldipine [6], nitrendipine [7, 8], PY 108–068 [2] and PN 200-110 [3] and three non-DHP Ca-antagonists, i.e., verapamil, diltiazem and KB-944 [9, 10].


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ebner F (1975) In: Lochner W, Braasch W, Kroneberg G (eds) 2nd International Adalat Symposium. New therapy of ischemic heart disease. Springer, Berlin Heidelberg New York, p 348.Google Scholar
  2. 2.
    Hof RP, Hof A, Neumann P (1982) J Cardiovasc Pharmacol 4:352.PubMedCrossRefGoogle Scholar
  3. 3.
    Hof RP, Hof A, Scholtysik G, Menninger K (1984) J Cardiovasc Pharmacol 6:407.PubMedCrossRefGoogle Scholar
  4. 4.
    Kazda S, Hoffmeister F (1979) Naunyn-Schmiedeberg’s Arch Pharmacol 307:R43.Google Scholar
  5. 5.
    Kazda S, Garthoff B, Krause HP, Schloßmann K (1982) Arzneim-Forsch 32:331.Google Scholar
  6. 6.
    Kazda S, Garthoff H, Meyer H, Schloßmann K, Stoepel K, Towart R, Vater W, Wehinger E (1980) Arzneim-Forsch 30:2144.Google Scholar
  7. 7.
    Meyer H, Bossert F, Wehinger E, Stoepel K, Vater W (1981) Arzneim-Forsch 31:407.Google Scholar
  8. 8.
    Knorr A, Stoepel K (1981) Arzneim-Forsch 31:2062.Google Scholar
  9. 9.
    Morita T, Yoshino K, Kanazawa T, Ito K, Nose T (1982) Arzneim-Forsch 32:1037.Google Scholar
  10. 10.
    Morita T, Kanazawa T, Ito K, Nose T (1982) Arzneim-Forsch 32:1043.Google Scholar
  11. 11.
    Endoh M, Hashimoto K (1970) Am J Physiol 218:1459.PubMedGoogle Scholar
  12. 12.
    Himori N, Ono H, Taira N (1976) Jpn J Pharmacol 26:427.PubMedCrossRefGoogle Scholar
  13. 13.
    Taira N, Kawada M, Satoh K (1983) J Cardiovasc Pharmacol 5:349.PubMedCrossRefGoogle Scholar
  14. 14.
    Satoh K, Yanagisawa T, Taira N (1981) Clin Exp Pharmacol Physiol 7:249.CrossRefGoogle Scholar
  15. 15.
    Satoh K, Kawada M, Wada Y, Taira N (1984) Arzneim-Forsch 34:563.Google Scholar
  16. 16.
    Takahashi K, Taira N (to be published) Arzneim-Forsch.Google Scholar
  17. 17.
    Satoh K, Wada Y, Taira N (1986) Arzneim-Forsch.Google Scholar
  18. 18.
    Wada Y, Satoh K, Taira N (1984) J Cardiovasc Pharmacol 6:881.PubMedCrossRefGoogle Scholar
  19. 19.
    Wada Y, Satoh K, Taira N (1985) J Cardiovasc Pharmacol 7:190.PubMedCrossRefGoogle Scholar
  20. 20.
    Endoh M, Kimura T, Hashimoto H (1974) Jpn J Pharmacol 24:771.CrossRefGoogle Scholar
  21. 21.
    Kubota K, Hashimoto K (1973) Naunyn-Schmiedeberg’s Arch Pharmacol 278:135.CrossRefGoogle Scholar
  22. 22.
    Hashimoto K, Iijima T, Hashimoto K, Taira N (1972) Tohoku J Exp Med 107:263.PubMedCrossRefGoogle Scholar
  23. 23.
    Ono H, Himori N, Taira N (1977) Tohoku J Exp Med 121:383.PubMedCrossRefGoogle Scholar
  24. 24.
    Narimatsu A, Taira N (1976) Naunyn-Schmiedeberg’s Arch Pharmacol 294:169.CrossRefGoogle Scholar
  25. 25.
    Endoh M, Yanagisawa T, Taira N (1978) Naunyn-Schmiedeberg’s Arch Pharmacol 302:235.CrossRefGoogle Scholar
  26. 26.
    Taira N (1979) In: Bing RJ (ed) New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium 1978. Excerpta Medica, Amsterdam Princeton, p 91.Google Scholar
  27. 27.
    Iijima T, Yanagisawa T, Taira N (1984) J Moll Cell Cardiol 16:1173.CrossRefGoogle Scholar
  28. 28.
    Sakamoto N, Terai M, Takenaka T, Maeno H (1978) Biochem Pharmacol 27:1269.PubMedCrossRefGoogle Scholar
  29. 29.
    Nishikori K, Takenaka T, Maeno H (1981) Jpn J Pharmacol 31:701.PubMedCrossRefGoogle Scholar
  30. 30.
    Norman JA, Ansell J, Phillips MA (1983) Eur J Pharmacol 93:107.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • N. Taira

There are no affiliations available

Personalised recommendations