Advertisement

Pharmakologisches Profil neuer Verapamil-Derivate

  • M. Raschack
  • J. Gries
  • W. Heimann
  • M. Kirchengast
  • C.-D. Müller
  • L. Szabo
  • H.-J. Teschendorf
  • L. Unger
Conference paper

Zusammenfassung

Anipamil, Emopamil und Devapamil sind neue Abkömmlinge von Verapamil (Isoptin), dem ersten klinisch genutzten Kalziumantagonisten. In der chemisch heterogenen Stoffklasse der Ca-Antagonisten ist Verapamil der Prototyp und gleichzeitig der therapeutisch wichtigste Vertreter der Untergruppe der Phenyl-alkylamine. Die Grundstruktur von Verapamil hat sich als ergiebige Quelle für Molekülabwandlungen mit interessanten Eigenschaften erwiesen.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Betz E, Hämmerle H, Kling D, Lenke D, Müller CD (1986) The actions of verapamil on the model of arteriosclerosis. In: J Rosenthal (Ed) Calcium antagonists and hypertension: current status. Excerpta Medica, 83–96Google Scholar
  2. 2.
    Betz E, Kling D (1987) The effect of anipamil on the permeability of arterial endothelium. Internat Symp on Calcium Antagonists, New York, February 10-13, Abstractbook 54Google Scholar
  3. 3.
    Bielenberg GW, Beck T, Haubruck H, Krieglstein J (1986) Effects of calcium entry blocker emopamil on postischemic energy metabolism of the isolated perfused rat brain and on local cerebral blood flow in the conscious rat. In: J Krieglstein (Ed) Pharmacology of cerebral ischemia. Elsevier Science Publishers Amsterdam New York Oxford, 309–315Google Scholar
  4. 4.
    Corsini A, Granata A, Fumagalli R, Paoletti R (1986) Calcium antagonists and low density lipoproteins metabolism by human fibroblasts and by human hepatoma cell line HEP G2. Pharmacol Res Comm 18: 1–16Google Scholar
  5. 5.
    Curtis MJ, Walker MJA, Yuswack T (1986) Actions of the verapamil analogues, anipamil and ronipamil, against ischaemia-induced arrhythmias in conscious rats. Br J Pharmac 88: 355–361Google Scholar
  6. 6.
    Denniss AR, Kingma JG, Hearse DJ, Downey JM, Yellon DM (1987) Anipamil limits myo-cardial necrosis without affecting hemodynamics in the closed chest dog during 24 hours of coronary artery occlusion. Eur Heart J (in press)Google Scholar
  7. 7.
    Dies R, Hahn KJ (1987) The blood pressure lowering effect of anipamil in mild to moderate hypertension. Internat Symp on Calcium Antagonists, New York, February 10–13, Abstract-book 70.Google Scholar
  8. 8.
    Ferrari R, Raddino R, Ceconi C, Curell S, Visioli O (1984) Protective effect of anipamil pre-treatment during myocardial ischaemia and reperfusion. Internat Symp on Calcium entry blockers and tissue protection, Rome, March 15-16, Abstractbook 32Google Scholar
  9. 9.
    Ferry DR, Goll A, Gadow C, Glossmann H (1984) (-)3H-desmethoxyverapamil labelling of putative calcium channels in brain: Autoradiographic distribution and allosteric coupling to 1,4-dihydropyridine and diltiazem binding sites. Naunyn-Schmiedebergs Arch Pharmacol 327: 183–187PubMedCrossRefGoogle Scholar
  10. 10.
    Fleet WF, Johnson TA, Graebner CA, Engle CL, Gettes LS (1986) Effects of verapamil on ischemia-induced changes in extracellular K+, pH, and local activation in the pig. Circulation 73: 837–846PubMedCrossRefGoogle Scholar
  11. 11.
    Fleckenstein A (1983) Calcium Antagonism in Heart and Smooth Muscle. Experimental Facts and Therapeutic Prospects. John Wiley & Sons New York Chichester Brisbane Toronto SingapurGoogle Scholar
  12. 12.
    Galizzi JP, Borsotto M, Barhanin J, Fosset M, Lazdunski M (1986) Characterization and Photoaffinity Labeling of Receptor Sites for the Ca2+ Channel Inhibitors d-cis-Diltiazem, (±)-Bepridil, Desmethoxyverapamil, and (+)-PN 200-110 in Skeletal Muscle Transverse Tubule Membranes. J Biol Chem 261: 1393–1397PubMedGoogle Scholar
  13. 13.
    Gerold M, Tschirky H (1968) Measurement of Blood Pressure in Unanaesthetized Rats and Mice. Arzneim Forsch 18: 1285–1287Google Scholar
  14. 14.
    Glossmann H, Ferry DR (1985) Assay for Calcium Channels. Methods in Enzymology 109: 513–550PubMedCrossRefGoogle Scholar
  15. 15.
    Glossmann H, Ferry DR, Goll A, Striessnig J, Zernig G (1985) Calcium Channels and Calcium Channel Drugs: Recent Biochemical and Biophysical Findings. Arzneim Forsch 35: 1917–1935Google Scholar
  16. 16.
    Gries J, Feilner K ( 1984) Untersuchungen zur blutdrucksenkenden Wirkung von Anipamil, einem neuen Ca-Antagonisten. Therapiewoche 34: 6390Google Scholar
  17. 17.
    Heimann W, Raschack M (1987) Protektive effect of the new calcium antagonist anipamil on isoproterenol-induced myocardial calcium overload and ultrastructural damage in the rat. J Mol Cell Cardiol (submitted)Google Scholar
  18. 18.
    Hill JL, Gettes LS (1980) Effect of Acute Coronary Artery Occlusion on Local Myocardial Extracellular K+-Activity in Swine. Circulation 61: 768–778PubMedGoogle Scholar
  19. 19.
    Hirche H, Friedrich R, Kebbel U, McDonald F, Zylka V (1982) Early Arrhythmias, Myocardial Extracellular Potassium and pH. In: JR Parratt (Ed) Early Arrhythmias resulting from Myocardial Ischaemia. MacMillan Press London, 113–124Google Scholar
  20. 20.
    Johnston KM, MacLeod BA, Walker MJA, (1983) Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics. Can J Physiol Pharmacol 61: 1340–1353PubMedCrossRefGoogle Scholar
  21. 21.
    Kirchengast M, Budden M, Zhang KM, Römer B, Martin C, Meesmann W (1984) Influence of the calcium-antagonist gallopamil (D 600) upon the increase of myocardial extracellular potassium activity during LAD-occlusion in dogs. Eur Heart J 5 (Suppl 1): 314Google Scholar
  22. 22.
    Kirchengast M, Raschack M (1986) Einfluß oraler Vorbehandlungen mit Anipamil auf funk-tionelle, biochemische und strukturelle Veränderungen nach Koronarokklusion an der Ratte. Unveröffentlichte ErgebnisseGoogle Scholar
  23. 23.
    Lenke D, Müller CD (1987) Inhibition of experimentally induced atherosclerosis by anipamil. Internat Symp on Calcium Antagonists, New York, February 10-13, Abstractbook 61Google Scholar
  24. 24.
    Lopez JF, Orchard RC (1985) Effects of verapamil on the extracellular K+ rise during myocardial ischaemia in dogs. Cardiovasc Res 19: 363–369PubMedCrossRefGoogle Scholar
  25. 25.
    Lossnitzer K, Mohr W, Konrad A, Guggenmoos R (1978) 3. Hereditary Cardiomyopathy in the Syrian Golden Hamster: Influence of Verapamil as Calcium Antagonist. In: M Kaltenbach, F Loogen, J Olsen (Eds) Cardiomyopathy and Myocarial Biopsy. Springer, Berlin Heidelberg New York, 27–37Google Scholar
  26. 26.
    Lossnitzer K, Steinhardt B, Grewe N, Stauch M (1975) Charakteristische Elektrolytveränderungen bei der erblichen Myopathie mit Kardiomyopathie des Syrischen Goldhamsters (Stamm BIO 8262). Basic Res Cardiol 70: 508–520PubMedCrossRefGoogle Scholar
  27. 27.
    Munson PJ, Rodbard D (1980) Ligand: A Versatile Computerized Approach for Characterization of Ligand-Binding Systems. Anal Biochem 107: 220–239PubMedCrossRefGoogle Scholar
  28. 28.
    Nawrath H, Raschack M (1984) Calcium antagonistic effects of the radioligand (−)-Desme-thoxyverapamil on cardiac and vascular smooth muscle preparations. Cell Calcium 5: 316CrossRefGoogle Scholar
  29. 29.
    Nawrath H, Raschack M (1987a) (−)-Devapamil decreases tension and calcium-45 uptake in smooth muscle preparations from rat aorta. Internat Symp on Calcium Antagonists, New York, February 10-–13 Abstractbook 36Google Scholar
  30. 30.
    Nawrath H, Raschack M (1987b) Effects of (—)-desmethoxyverapamil on heart and vascular smooth muscle. J Pharm Exp Ther (accepted)Google Scholar
  31. 31.
    Raschack M (1984a) Anipamil, a novel calcium antagonist with long-lasting oral efficacy, as assessed against hypoxic and ischemic damage of heart and kidney. Internat Symp on Calcium entry blockers and tissue protection, Rome, March 15-16, Abstractbook 34Google Scholar
  32. 32.
    Raschack M (1984b) Anipamil, ein neuer Calcium-Antagonist mit langanhaltender kardiopro-tektiver Wirkung. Z Kardiol 73 (Suppl 1): 67Google Scholar
  33. 33.
    Raschack M (1984c) Prolonged cardioprotective effects of anipamil, a new calcium antagonist. Eur Heart J 5 (Suppl 1): 10Google Scholar
  34. 34.
    Raschack M, Gries J (1986) Cardioprotective and antihypertensive effects of the new calcium antagonist anipamil in rats and hamsters. J Mol Cell Cardiol 18 (Suppl 1): 119Google Scholar
  35. 35.
    Raschack M, Gries J, Kapp W, Maurer R (1984) Prevention by chronic oral anipamil of calcium overload and necroses in hearts of cardiomyopathic Syrian hamsters as well as progression of hypertension and early mortality in stroke-prone rats. Internat Symp on Calcium Entry Blockers and Tissue Protection, Rome, March 15-16, Abstractbook 100Google Scholar
  36. 36.
    Raschack M, Kapp W, Heimann W (1984) Oral anipamil prevents myocardial Ca-overload and necroses in cardiomyopathic hamsters. J Mol Cell Cardiol 16 (Suppl 1): 62CrossRefGoogle Scholar
  37. 37.
    Raschack M, Kirchengast M (1986) Inhibition by anipamil of epicardial ST elevation and K+-liberation after coronary artery occlusion in pigs. J Mol Cell Cardiol 18 (Suppl 2): 142Google Scholar
  38. 38.
    Rouleau JL, Parmley WW, Stevens J, Wikman-Coffelt J, Sievers R, Mahley RW, Havel RJ (1983) Verapamil Suppresses Atherosclerosis in Cholesterol-Fed Rabbits. J Am Coll Cardiol 1: 1453–1460PubMedCrossRefGoogle Scholar
  39. 39.
    Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 234: H59-H66Google Scholar
  40. 40.
    Wagner JA, Reynolds IJ, Weisman HF, Dudeck P, Weisfeldt ML, Snyder SH (1986) Calcium Antagonist Receptors in Cardiomyopathic Hamster: Selective Increases in Heart, Muscle, Brain. Science 232: 515–516PubMedCrossRefGoogle Scholar
  41. 41.
    Wiegand V, Güggi M, Meesmann W, Kessler M, Greitschus F (1979) Extracellular potassium activity changes in the canine myocardium after acute coronary occlusion and the influence of beta-blockade. Cardiovasc Res 13: 297–302PubMedCrossRefGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1988

Authors and Affiliations

  • M. Raschack
    • 1
  • J. Gries
    • 1
  • W. Heimann
    • 1
  • M. Kirchengast
    • 1
  • C.-D. Müller
    • 1
  • L. Szabo
    • 1
  • H.-J. Teschendorf
    • 1
  • L. Unger
    • 1
  1. 1.Department Herz-Kreislauf-PharmakologieForschung und Entwicklung, Knoll AG LudwigshafenLudwigshafenDeutschland

Personalised recommendations