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Thromb Haemost 1976; 36(02): 376-387
DOI: 10.1055/s-0038-1648052
Original Article
Schattauer GmbH

Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

Teruhiko Umetsu
1   Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2–28–8, Bunkyo-ku, Tokyo, Japan
,
Kazuko Sanai
1   Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2–28–8, Bunkyo-ku, Tokyo, Japan
,
Tadakatsu Kato
1   Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2–28–8, Bunkyo-ku, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Received 06 February 1976

Accepted 02 June 1976

Publication Date:
03 July 2018 (online)

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Summary

The effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.

Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.

From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

 

  • References

  • 1 Abudulla Y. H. 1969; β-Adrenergic receptors in human platelets. Journal of Atherosclerosis Research 9: 171.
    CrossrefPubMedGoogle Scholar
  • 2 Barthel W, Markwardt F. 1974; Aggregation of blood platelets by biogenic amines and its inhibition by anti-adrenergic and anti-serotoninergic agents. Biochemical Pharmacology 23: 37.
    CrossrefPubMedGoogle Scholar
  • 3 Born G. V. R. 1962; Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194: 972.
    PubMedGoogle Scholar
  • 4 Brecher G, Cronkite E. P. 1950; Morphology and enumeration of human blood platelets. Journal of Applied Physiology 3: 365.
    CrossrefPubMedGoogle Scholar
  • 5 Bygdeman S, Johnson O. 1969; Studies on the effect of adrenergic blocking drugs on catecholo-mine-induced platelet aggregation and uptake of noradrenaline and 5-hydrosytryptamine. Acta Phy-siologica Scandinavia 75: 129.
    CrossrefPubMedGoogle Scholar
  • 6 Dreyfuss F, Zahavi J. 1973; Adenosine diphosphate induced platelet aggregation in myocardial infarction and ishemic heart disease. Atherosclerosis 17: 107.
    CrossrefPubMedGoogle Scholar
  • 7 Gibelli G, Montanari C, Bellan D, Mandelli V, Sacchetti G. 1973; Beta-blocking drugs and human platelet aggregation in vitro. Experientia 29: 186.
    CrossrefPubMedGoogle Scholar
  • 8 Haerem J. W. 1974; Mural platelet microthrombi and major acute lesions of main epicardial arteries in sudden coronary death. Atherosclerosis 19: 529.
    CrossrefPubMedGoogle Scholar
  • 9 Haft J.L, Gershengorn K, Kranz P. D, Oestreicher R. 1972a Protection against epinephrine-induced myocardial necrosis by drugs that inhibit platelet aggregation. American Journal of Cardiology 30: 838.
    PubMedGoogle Scholar
  • 10 Haft J. I, Kranz P. D, Albert F. J, Fani K. 1972b Intravascular platelet aggregation in the heart induced by norepinephrine. Microscopic studies. Circulation 46: 698.
    PubMedGoogle Scholar
  • 11 Lemmer B, Wiethold G, Hellenbrecht D, Bak I. J, Grobcker H. 1972; Human blood platelets as cellular models for investigation of membrane active drugs: Beta-adrenergic blocking agents. Naunyn-Schmiedeberg’s Archiv für Pharmakologie 275: 299.
    PubMedGoogle Scholar
  • 12 Matsuda T. 1973; Arteriosclerosis and thrombosis. Rinsho Byori 21: 886.
    PubMedGoogle Scholar
  • 13 McNicol G. P, Mitchell J. R. A, Reuter H, Loo J. V. D. 1974; Platelets in thrombosis. Their clinical significance and the evaluation of potential drugs. Thrombosis et Diathesis Haemorrhagica 31: 379.
    PubMedGoogle Scholar
  • 14 Mills D. C. B, Roberts G. C. K. 1967; Effects of adrenaline on human blood platelets. Journal of physiology 193: 443.
    CrossrefPubMedGoogle Scholar
  • 15 O’Brien J. R, Etherington M, Jamieson S, Klaber M. R, Lincoln S. V. 1974; Platelets function long after arterial and venous thrombosis. Thrombosis et Diathesis Haemorrhagica 31: 279.
    PubMedGoogle Scholar
  • 16 Salzman E. W. 1963; Measurement of platelet adhesiveness. A simple in vitro technique demonstrating an abnormality in von Willebrand’s disease. Journal of Laboratory and Clinical Medicine 62: 724.
    PubMedGoogle Scholar
  • 17 Sano T, Yokoyama M. 1971; Effect of pyridinolcarbamate on platelet aggregation. American Journal of Medical Sciences 262: 205.
    CrossrefPubMedGoogle Scholar
  • 18 Shimamoto T, Yamazaki H, Inoue M, Fujita T, Sagawa N, Ishioka T, Sunaga T. 1960; Effect of adrenaline and noadrenaline on “silicone-like property” of blood vessels. Proceedings of the Japan Academy 36: 234.
    CrossrefPubMedGoogle Scholar
  • 19 Shimamoto T. 1963; The relationship of edematous reaction in arteries to atherosclerosis and thrombosis. Journal of Atherosclerosis Research 3: 87.
    CrossrefPubMedGoogle Scholar
  • 20 Sinakos Z, Caen J. P. 1967; Platelet aggregation in mammalians (human, rat, rabbit, guineapig, horse, dog). A comparative study. Thrombosis et Diathesis Haemorrhagica 17: 99.
    PubMedGoogle Scholar
  • 21 Spaet T. H, Stemerman M. B. 1972. Platelet adhesion. In: Weiss H. J. (ed). Platelets and their Role in Hemostasis. Annals of New York Academy of Sciences. 201 13.
    Google Scholar
  • 22 Umetsu T, Kato T. 1973; Biochemical studies on a new β-receptor blocking agent, l-(tert-butylamino)-3-(2-chloro-5-methylphenoxy)-2-propanol (2) Effect of KL 255 on ADP-induced rabbit platelet aggregation. Pharmacometrics 7: 31.
    PubMedGoogle Scholar
  • 23 Yamazaki H, Odakura T, Takeuchi K, Sano T. 1970; Adhesive platelet count and blood coagulability in myocardial infarction and cerebral thrombosis. Thrombosis et Diathesis Haemorrhagica 24: 450.
    PubMedGoogle Scholar
  • 24 Yamazaki H, Sano T, Odakura T, Takeuchi K, Matsumura T, Hosaki S, Shimamoto T. 1971; Appearance of thrombogenic tendency induced by adrenaline and its prevention by β-adrenergic blocking agent, nialamide and pyridinolcarbamate. Thrombosis et Diathesis Haemorrhagica 26: 251.
    PubMedGoogle Scholar
  • 25 Yamazaki H, Kobayashi L, Sano T, Shimamoto T. 1973; Enhancement of ADP-induced platelet aggregation by adrenaline in vivo and its prevention. Thrombosis et Diathesis Haemorrhagica 29: 490.
    PubMedGoogle Scholar
  • 26 Yamazaki H. 1973; Platelet functions in thromboembolic disorders. Rinsho Byori 21: 892.
    PubMedGoogle Scholar