Advertisement

Allgemeine Pharmakologie von Beta-Adrenoceptorantagonisten

  • B. Åblad
  • E. Carlsson
  • L. Ek
  • G. Johnsson
  • B. Lundgren
Conference paper
  • 15 Downloads

Zusammenfassung

Im Jahre 1948 stellte Ahlquist die Behauptung auf, daß die adrenerge Transmittorsubstanz Noradrenalin ihre Effekte durch die Verbindung mit zwei verschiedenen Arten von Rezeptoren — Alpha und Beta — hervorruft (5). Jüngere Studien haben ergeben, daß Beta-Adrenozeptoren keine homogene Gruppe bilden. Lands u. Mitarb, haben im Jahre 1967 eine Unterteilung in Beta-1- und Beta-2-Rezeptoren vorgeschlagen (27). Abbildung 1 zeigt einige adrenerge Wirkungen und den Rezeptortyp, der bei der Übertragung dieser einzelnen Effekte hauptsächlich beteiligt ist. Alpha-Rezeptoren übertragen beispielsweise die Konstriktion der glatten Muskeln in den Blutgefäßen und im Uterus. Beta-1-Rezeptoren vermittein die Stimulierung des Herzens, aber auch andere Wirkungen wie Lipolyse und Reninfreisetzung. Beta-2-Rezeptoren vermitteln die Erschlaffung der glatten Muskeln, beispielsweise in den Blutgefäßen, Bronchien und im Uterus, weiters verschiedene metabolische Effekte, wie die Insulinfreisetzung von den Beta-Zellen im Pankreas, Die hier angeführten Effekte sind nur eine kleine Auswahl der Prozesse, die durch das adrenerge Nervensystem kontrolliert werden. Nach der Einteilung von Lands u. Mitarb. (27) in Beta-1/Beta-2-Rezeptoren gibt es jetzt drei Gruppen von Beta-Rezeptoragonisten und -antagonisten.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Åblad, B., Carlsson, E., Ek, L.: Pharmacological studies of two cardioselective adrenergic β-receptor antagonists. Life Sci. 12, 107 (1973)CrossRefGoogle Scholar
  2. 2.
    Åblad, B., Carlsson, B., Carlsson, E., Dahlöf, C., Ek, L., Hultberg, E.: Cardiac effects of β-adrenergic receptor antagonists. The Myocardium. Adv. Cardiol. 12, 290 (1974a)Google Scholar
  3. 3.
    Åblad, B., Borg, K.O., Johnsson, B., Regårdh, C.-G., Sölvell, L.: Combined pharmacokinetic and pharmacodynamic studies on alprenolol und 4-hydroxy-alprenolol in man. Life Sci. 14, 693 (1974b)PubMedCrossRefGoogle Scholar
  4. 4.
    Åblad, B., Borg, K.O., Carlsson, E., Ek, L., Johnsson, G., Malmfors, T., Regårdh, C.-G.: A survey of the pharmacological properties of metoprolol in animals and man. Acta Pharmacol. Toxicol. (Kbh) 36 (Suppl. 5), 7 (1975)CrossRefGoogle Scholar
  5. 5.
    Ahlquist, R.P.: A study of the adrenotropic receptors. Am. J. Physiol. 153, 586 (1948)PubMedGoogle Scholar
  6. 6.
    Barrett, A.M., Carter, J., Fitzgerald, J.D., Hull, R., Le Count, D.: A new type of cardioselective adrenoceptive blocking drug. Br. J. Pharmacol. 48, 340P (1973)PubMedGoogle Scholar
  7. 7.
    Bengtsson, C., Johnsson, G., Regårdh, C.-G.: Plasma levels and effects of metoprolol on blood pressure and heart rate in hypertensive patients after an acute dose and between two doses during long-term treatment. Clin. Pharmacol. Ther. 17, 400 (1975)PubMedGoogle Scholar
  8. 8.
    Bowman, W.C., Nott, M.W.: Actions of some sympathomimetic bronchodilator and beta-adrenoceptor blocking drugs on contractions of the cat soleus muscle. Br. J. Pharmacol. 38, 37 (1970)PubMedGoogle Scholar
  9. 9.
    Brittain, R.T., Farmer, J.B., Jack, D., Martin, L.-E., Simson, W.T.: Alpha-(t-butylamino)methyl-4-hydrocy-m-xylene-α12-diol (AH3365): A selective β-adrenergic stimulant. Nature 219, 862 (1968)PubMedCrossRefGoogle Scholar
  10. 10.
    Callingham, B.A.: The Catecholamines. Adrenaline, noradrenalin. In: Hormones in blood, Vol. 2. Gray, Bacharach, (eds.), p. 519. London: Academic Press 1967Google Scholar
  11. 11.
    Carlsson, E.: Differentiated blockade of the chronotropic effects of various stimuli in the cat heart. Acta Pharmacol. Toxicol. (Kbh) 31 (Suppl. 1), 63 (1972)Google Scholar
  12. 12.
    Carlsson, E., Carlsson, B.: Evidence for two β-receptor populations mediating the same adrenergic response in the cat heart (in Druck)Google Scholar
  13. 13.
    Carlsson, E., Ablad, B., Brändström, A., Carlsson, B.: Differentiated blockade of the chronotropic effects of various adrenergic stimuli in the heart. Life Sci. 11, 953 (1972)CrossRefGoogle Scholar
  14. 14.
    Carlsson, E., Dahlöf, C.-G., Hedberg, A., Persson, H., Tangstrand, B.: Differentiation of cardiac chronotropic and inotropic effects of β-adrenoceptor agonists. Arch. Pharmacol. 300, 101 (1977)CrossRefGoogle Scholar
  15. 15.
    Cerasi, E., Luft, R., Efendic, S.: Effect of adrenergic blocking agents on insulin response to glucose infusion in man. Acta Endocrin. 69, 335 (1972)Google Scholar
  16. 16.
    Cleaveland, C.R., Shand, D.G.: Effect of route of administration on the relationship between β-adrenergic blockade and plasma propranolol level. Clin. Pharmacol. Ther. 13, 181 (1972)PubMedGoogle Scholar
  17. 17.
    Davidson, N. McD., Corrall, R.J.M., Shaw, T.R.D., French, E.B.: Observations in man of hypoglycemia during selective and non-selective β-blockade. Scott. Med. J. 22, 69 (1977)PubMedGoogle Scholar
  18. 18.
    Dunlop, D., Shanks, R.G.: Selective blockade of adrenoceptive beta receptors in the heart. Br. J. Pharmacol. Chemother. 32, 201 (1968)PubMedGoogle Scholar
  19. 19.
    Ek, L., Björkman, J.-A., Carlsson, E.: Cardiovascular effects of nonselective and β1-selective adrenoceptor antagonists in anaesthetized dogs, (im Druck)Google Scholar
  20. 20.
    Fitzgerald, J.D.: The role of beta-adrenergic blockade in acute myocardial ischaemia. In: Effect of acute ischaemia on myocardial function. Oliver, M.F., Julian, D.G., Donald, K.W. (eds.), p. 321. Edinburgh, London: Churchill Livingstone 1972Google Scholar
  21. 21.
    Formgren, H.: The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics. Br. J. Clin. Pharmac. 3, 1007 (1976)Google Scholar
  22. 22.
    Furchgott, R.F.: Postsynaptic adrenergic receptor mechanisms in vascular smooth muscle. In: Vascular neuroeffector mechanisms. 2. Int. Symp. Odense, 1975, S. 131. Basel: Karger 1976Google Scholar
  23. 23.
    Gibson, D.G.: Pharmacodynamic properties of β-adrenergic receptor blocking drugs in man. Drugs 7, 8 (1974)PubMedCrossRefGoogle Scholar
  24. 24.
    Johnsson, G.: Influence of metoprolol and propranolol on hemodynamic effects induced by adrenaline and physical work. Acta Pharmacol. Toxicol. (Kbh) 36 (Suppl. 5), 59 (1975)CrossRefGoogle Scholar
  25. 25.
    Johnsson, G., Regårdh, C.-G.: Clinical pharmacokinetics of β-adrenoceptor blocking drugs. Clin. Pharmacokin. 1, 233 (1976)CrossRefGoogle Scholar
  26. 26.
    Johnsson, G., Nyberg, G., Sölvell, L.: Influence of metoprolol and propranolol on hemodynamic effects induced by physical work and isoprenaline. Acta Pharmacol. Toxicol. (Kbh) 36 (Suppl. 5), 69 (1975)CrossRefGoogle Scholar
  27. 27.
    Lands, A.M., Arnold, A., McAuliff, J.P., Luduena, F.P., Brown, Jr., T.G.: Differentiation of receptor systems activated by sympathomimetic amines. Nature 214, 597 (1967)PubMedCrossRefGoogle Scholar
  28. 28.
    Levy, B., Wilkenfeld, B.E.: An analysis of selective beta receptor blockade. Eur. J. Pharmacol. 5, 227 (1968/69)CrossRefGoogle Scholar
  29. 29.
    Loubatieres, A., Mariani, M.M., Sorel, B., Savi, L.: The action of 3-adrenergic blocking and stimulating agents on insulin secretion. Characterisation of the type of β-receptor. Diabetologia 7, 127 (1971)PubMedCrossRefGoogle Scholar
  30. 30.
    Lundgren, B., Carlsson, E., Herrmann, I.: Effects of propranolol metoprolol and atenolol on isoprenaline induced tachycardia bronchorelaxation and vasodilatation in the anaesthetized cat. 1979 (im. Druck)Google Scholar
  31. 31.
    Persson, H., Olsson, T.: Some pharmacological properties of Terbutaline (INN), 1-(3.5-dihydroxyphenyl)-2-(T-butylamino)-etanol. A new sympathomimetic β-receptor-stimulating agent. Acta Med. Scand. 1970 (Suppl. 512), 11Google Scholar
  32. 32.
    Scales, B., Cosgrove, M.B.: The metabolism and distribution of the selective adrenergic beta blocking agent, practolol. J. Pharmacol. Exp. Ther. 175, 338 (1970)PubMedGoogle Scholar
  33. 33.
    Thiringer, G., Svedmyr, N.: Interaction of orally administered metoprolol, practolol and propranolol with isoprenaline in asthmatics. Eur. J. Clin. Pharmacol. 10, 163 (1976)CrossRefGoogle Scholar
  34. 34.
    Tivenius, L.: Effects of multiple doses of metoprolol and propranolol on ventilatory function in patients with chronic obstructive lung disease. Scand. J. Respir. Dis. 57, 190 (1976)PubMedGoogle Scholar
  35. 35.
    VanDeripe, D.R., Ablad, B., Moran, N.C.: β-adrenergic receptor blockade by four methyl substitute N-isopropylphenylethanolamines. Fed. Proc. 23, 124 (1964)Google Scholar
  36. 36.
    Vendsalu, A.: Studies on adrenaline and noradrenaline in human plasma. Acta Physiol. Scand. 49 (Suppl. 173), 1960Google Scholar
  37. 37.
    Waal-Manning, H.J., Simpson, F.O.: Practolol treatment in asthmatics. Lancet 1971 II, 1264CrossRefGoogle Scholar
  38. 38.
    Waal-Manning, H.J.: Metabolic effects of β-adrenoceptor blockers. Drugs 11 (Suppl. 1), 121 (1976)PubMedCrossRefGoogle Scholar
  39. 39.
    Wasserman, M.A., Levy, B.: Selective beta adrenergic receptor antagonism in the anaesthetized dog. J.. Pharmacol. Exp. Ther. 188, 357 (1974PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1979

Authors and Affiliations

  • B. Åblad
  • E. Carlsson
  • L. Ek
  • G. Johnsson
  • B. Lundgren
    • 1
  1. 1.Forschungslaboratorien und Medizinische AbteilungAB HässleS-MölndalSchweden

Personalised recommendations