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. 1985 May;85(1):255–262. doi: 10.1111/j.1476-5381.1985.tb08854.x

A comparison of several calcium antagonists on uterine, vascular and cardiac muscles from the rat.

S E Granger, M Hollingsworth, A H Weston
PMCID: PMC1916761  PMID: 4027468

Abstract

An assessment was made of the potencies of nifedipine, gallopamil, diltiazem, cinnarizine and salbutamol as inhibitors of tension development by the uterus and cardiovascular tissues from the term pregnant rat. The rank order of potency was nifedipine greater than gallopamil greater than diltiazem for those preparations on which these compounds were potent, viz. spontaneous and oxytocin-induced tension development of the uterus, spontaneous tension development of hepatic portal vein, potassium chloride (KCl)-induced pressure rises of perfused mesenteric bed and electrically-stimulated (0.5 Hz) ventricular muscle. The rank order of potency of nifedipine, gallopamil and diltiazem was different for those preparations on which they exhibited low potency, viz. noradrenaline-induced pressure rises of perfused mesenteric bed and tension development of aorta. Gallopamil and diltiazem, but not nifedipine, were more potent against tension development by ventricular muscle stimulated at 2.5 Hz than at 0.5 Hz, suggesting that nifedipine interacts at a different site from the other compounds. Cinnarizine was less potent than the other calcium antagonists on the uterus and portal vein, was the second most potent compound against KCl-induced pressure rises of the mesenteric bed and was equipotent against responses to noradrenaline and KCl of the mesenteric bed (unlike the other compounds). This suggests that the site of action of cinnarizine differs from that of the other calcium antagonists. Nifedipine, gallopamil and diltiazem, like salbutamol, exhibited selectivity for inhibition of tension development by the uterus relative to the cardiovascular tissues.

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Selected References

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  1. Andersson K. E., Edvinsson L., MacKenzie E. T., Skärby T., Young A. R. Influence of extracellular calcium and calcium antagonists on contractions induced by potassium and prostaglandin F2 alpha in isolated cerebral and mesenteric arteries of the cat. Br J Pharmacol. 1983 May;79(1):135–140. doi: 10.1111/j.1476-5381.1983.tb10505.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  3. Colquhoun D., Sheridan R. E. The effect of tubocurarine competition on the kinetics of agonist action on the nicotinic receptor. Br J Pharmacol. 1982 Jan;75(1):77–86. doi: 10.1111/j.1476-5381.1982.tb08759.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Csapo A. I., Puri C. P., Tarro S., Henzl M. R. Deactivation of the uterus during normal and premature labor by the calcium antagonist nicardipine. Am J Obstet Gynecol. 1982 Mar 1;142(5):483–491. doi: 10.1016/0002-9378(82)90749-9. [DOI] [PubMed] [Google Scholar]
  5. Fleckenstein A., Fleckenstein-Grün G. Cardiovascular protection by Ca antagonists. Eur Heart J. 1980 Dec;1(Suppl B):15–21. doi: 10.1093/eurheartj/1.suppl_2.15. [DOI] [PubMed] [Google Scholar]
  6. Fleckenstein A., Grün G., Tritthart H., Byon K. Uterus-Relaxation durch hochaktive Ca plus,plus-antagonistische Hemmstoffe der elektro-mechanischen Koppelung wie Isoptin (Verapamil, Iproveratril), Substanz D 600 und Segontin (Prenylamin). Versuche am isolierten Uterus virgineller Ratten. Klin Wochenschr. 1971 Jan;49(1):32–41. doi: 10.1007/BF01494064. [DOI] [PubMed] [Google Scholar]
  7. Forman A., Andersson K. E., Ulmsten U. Inhibition of myometrial activity by calcium antagonists. Semin Perinatol. 1981 Jul;5(3):288–294. [PubMed] [Google Scholar]
  8. Godfraind T. Actions of nifedipine on calcium fluxes and contraction in isolated rat arteries. J Pharmacol Exp Ther. 1983 Feb;224(2):443–450. [PubMed] [Google Scholar]
  9. Godfraind T. Mechanisms of action of calcium entry blockers. Fed Proc. 1981 Dec;40(14):2866–2871. [PubMed] [Google Scholar]
  10. Godfraind T., Miller R. C. Actions of prostaglandin F2 alpha and noradrenaline on calcium exchange and contraction in rat mesenteric arteries and their sensitivity to calcium entry blockers. Br J Pharmacol. 1982 Jan;75(1):229–236. doi: 10.1111/j.1476-5381.1982.tb08777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Holck M., Thorens S., Haeusler G. Characterization of [3H]nifedipine binding sites in rabbit myocardium. Eur J Pharmacol. 1982 Dec 3;85(3-4):305–315. doi: 10.1016/0014-2999(82)90217-5. [DOI] [PubMed] [Google Scholar]
  12. Hollingsworth M., Schnieden H. Letter: Salbutamol and inhibition of uterine contractions. J Pharm Pharmacol. 1973 Dec;25(12):996–998. doi: 10.1111/j.2042-7158.1973.tb09992.x. [DOI] [PubMed] [Google Scholar]
  13. Imaizumi Y., Watanabe M. The effect of tetraethylammonium chloride on potassium permeability in the smooth muscle cell membrane of canine trachea. J Physiol. 1981 Jul;316:33–46. doi: 10.1113/jphysiol.1981.sp013770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jim K., Harris A., Rosenberger L. B., Triggle D. J. Stereoselective and non-stereoselective effects of D 600 (methoxyverapamil) in smooth muscle preparations. Eur J Pharmacol. 1981 Nov 19;76(1):67–72. doi: 10.1016/0014-2999(81)90010-8. [DOI] [PubMed] [Google Scholar]
  15. Johnson J. D., Fugman D. A. Calcium and calmodulin antagonists binding to calmodulin and relaxation of coronary segments. J Pharmacol Exp Ther. 1983 Aug;226(2):330–334. [PubMed] [Google Scholar]
  16. Karaki H., Nakagawa H., Urakawa N. Comparative effects of verapamil and sodium nitroprusside on contraction and 45Ca uptake in the smooth muscle of rabbit aorta, rat aorta and guinea-pig taenia coli. Br J Pharmacol. 1984 Feb;81(2):393–400. doi: 10.1111/j.1476-5381.1984.tb10091.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liggins G. C., Vaughan G. S. Intravenous infusion of salbutamol in the management of premature labour. J Obstet Gynaecol Br Commonw. 1973 Jan;80(1):29–32. doi: 10.1111/j.1471-0528.1973.tb02126.x. [DOI] [PubMed] [Google Scholar]
  18. MCGREGOR D. D. THE EFFECT OF SYMPATHETIC NERVE STIMULATION OF VASOCONSTRICTOR RESPONSES IN PERFUSED MESENTERIC BLOOD VESSELS OF THE RAT. J Physiol. 1965 Mar;177:21–30. doi: 10.1113/jphysiol.1965.sp007572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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 Aug;25(4):383–392. doi: 10.1254/jjp.25.383. [DOI] [PubMed] [Google Scholar]
  20. Narimatsu A., Taira N. Effects of 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 preparation of the dog. Naunyn Schmiedebergs Arch Pharmacol. 1976 Aug;294(2):169–177. doi: 10.1007/BF00507850. [DOI] [PubMed] [Google Scholar]
  21. Nayler W. G., Horowitz J. D. Calcium antagonists: a new class of drugs. Pharmacol Ther. 1983;20(2):203–262. doi: 10.1016/0163-7258(83)90040-2. [DOI] [PubMed] [Google Scholar]
  22. Nishikori K., Takenaka T., Maeno H. A possible mechanism for relaxation of rat uterine smooth muscle by nicardipine hydrochloride (YC-93), a new potent vasodilator. Jpn J Pharmacol. 1981 Oct;31(5):701–709. doi: 10.1254/jjp.31.701. [DOI] [PubMed] [Google Scholar]
  23. Reiner O., Marshall J. M. Action of D-600 on spontaneous and electrically stimulated activity of the parturient rat uterus. Naunyn Schmiedebergs Arch Pharmacol. 1975;290(1):21–28. doi: 10.1007/BF00499986. [DOI] [PubMed] [Google Scholar]
  24. Spedding M. Assessment of "Ca2+ -antagonist" effects of drugs in K+ -depolarized smooth muscle. Differentiation of antagonist subgroups. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):234–240. doi: 10.1007/BF00500485. [DOI] [PubMed] [Google Scholar]
  25. Spedding M. Changing surface charge with salicylate differentiates between subgroups of calcium-antagonists. Br J Pharmacol. 1984 Sep;83(1):211–220. doi: 10.1111/j.1476-5381.1984.tb10137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Van Nueten J. M., Vanhoutte P. M. Calcium entry blockers and vascular smooth muscle heterogeneity. Fed Proc. 1981 Dec;40(14):2862–2865. [PubMed] [Google Scholar]

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