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Thromb Haemost 1973; 30(02): 315-326
DOI: 10.1055/s-0038-1649080
Original Article
Schattauer GmbH

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo[*]

J. Heinz Joist
1   Department of Pathology, McMaster University, Hamilton, Ontario, Canada
2   Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
,
Jean-Pierre Cazenave
1   Department of Pathology, McMaster University, Hamilton, Ontario, Canada
2   Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
,
J. Fraser Mustard
1   Department of Pathology, McMaster University, Hamilton, Ontario, Canada
2   Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Received for publication 13 April 1973

Accepted for publication 16 July 1973

Publication Date:
30 June 2018 (online)

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Summary

Sodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

* Presented in part at the II. Congress of the International Society on Thrombosis and Hemostasis, Oslo, Norway, August, 1971.


 

  • References

  • 1 Aldridge W. N. 1962. Action of barbiturates upon respiratory enzymes. In: Mongar J. L, and de Reuck A. V. S. (eds.) Enzymes and Drug Action (Ciba Foundation Symposium),. Boston/London: Little, Brown and Co., Churchill;
    Search in Google Scholar
  • 2 Aledort L. M, and Niemetz J. 1968; Dissociation of platelet aggregation from clot retraction, potassium loss and adenosine triphosphatase activity. Proceedings of the Society of Experimental Biology and Medicine 128: 658.
    PubMedSearch in Google Scholar
  • 3 Ardlie N. G, Packham M. A, and Mustard J. F. 1970; Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. British Journal of Haematology 19: 7.
    CrossrefPubMedSearch in Google Scholar
  • 4 Born G. V. R. 1970; Observations on the change in shape of blood platelets brought about by adenosine diphosphate. Journal of Physiology 209: 487.
    CrossrefPubMedSearch in Google Scholar
  • 5 Brodie B. B, Burns J. J, Mark L. C, Lief P. A, Bernstein E, and Papper E. M. 1953; The fate of pentobarbital in man and dog and a method for its estimation in biological material. Journal of Pharmacology and Experimental Therapeutics 109: 26.
    PubMedSearch in Google Scholar
  • 6 Butler T. C. 1950; Theories of general anesthesia. Pharmacological Reviews 2: 121.
    PubMedSearch in Google Scholar
  • 7 Cazenave J.-P, Packham M. A, Guccione M. A, and Mustard J. F. 1973; Effects of penicillin G on platelet aggregation, release and adherence to collagen. Proceedings of the Society of Experimental Biology and Medicine 142: 159.
    PubMedSearch in Google Scholar
  • 8 Chance B, Hollunger G, and Hagihara B. 1962; Inhibition of energy transfer at the pyridine nucleotide-flavin site. Biochemical and Biophysical Research Communications 8: 180.
    CrossrefPubMedSearch in Google Scholar
  • 9 Gillett R, and Warburton F. G. 1970; Barbiturate blood levels found at necropsy in proven cases of acute barbiturate poisoning. Journal of Clinical Pathology 23: 435.
    CrossrefPubMedSearch in Google Scholar
  • 10 Lucas O. N, Millar G. J, and Jaques L. B. 1967; Spontaneous hemorrhage in anticoagulant-treated rats when subjected to excitant or depressant drugs. Thrombosis et Diathesis Haemorrhagica 17: 561.
    PubMedSearch in Google Scholar
  • 11 Joist J. H, Kinlough-Rathbone R. L, Packham M. A, and Mustard J. F. (in preparation): Inhibition of platelet energy metabolism by sodium pentobarbital and its effect on platelet function.
    PubMed
  • 12 Kinlough-Rathbone R. L, Packham M. A, and Mustard J. F. 1970; The effect of glucose on adenosine diphosphate-induced platelet aggregation. Journal of Laboratory and Clinical Medicine 75: 780.
    PubMedSearch in Google Scholar
  • 13 McElroy F. A, Kinlough-Rathbone R. L, Ardlie N. G, Packham M. A, and Mustard J. F. 1971; The effect of aggregating agents on oxidative metabolism of rabbit platelets. Biochimica et Biophysica Acta 253: 64.
    CrossrefPubMedSearch in Google Scholar
  • 14 McIlwain H. 1962. Appraising enzymic actions of central depressants by examining cerebral tissues. In: Mongar J. L, and de Reuck A. V. S. (eds.) Enzymes and Drug Action (Ciba Foundation Symposium),. Boston/London: Little, Brown and Co., Churchill;
    Search in Google Scholar
  • 15 McKenzie F. N, Svensjö E, and Arfors K. E. 1972; Effect of sodium pentobarbital anesthesia on platelet behaviour in vitro and in vivo. Microvascular Research 4: 42.
    CrossrefPubMedSearch in Google Scholar
  • 16 Movat H. Z, Weiser W. J, Glynn M. F, and Mustard J. F. 1965; Platelet phagocytosis and aggregation. Journal of Cell Biology 27: 531.
    CrossrefPubMedSearch in Google Scholar
  • 17 Murer E. H. 1968; Release reaction and energy metabolism in blood platelets with special reference to the burst in oxygen uptake. Biochimica et Biophysica Acta 162: 320.
    CrossrefPubMedSearch in Google Scholar
  • 18 Murer E. H, Hellem A. J, and Rozenberg M. D. 1967; Energy metabolism and platelet function. Scandinavian Journal of Clinical and Laboratory Investigation 19: 280.
    CrossrefPubMedSearch in Google Scholar
  • 19 Mustard J. F, and Packham M. A. 1970; Factors influencing platelet function: adhesion, release and aggregation. Pharmacological Reviews 22: 97.
    PubMedSearch in Google Scholar
  • 20 Mustard J. F, Hegardt B, Rowsell H. C, and Mac Millan R. L. 1964; Effect of adenosine nucleotides on platelet aggregation and clotting time. Journal of Laboratory and Clinical Medicine 64: 548.
    PubMedSearch in Google Scholar
  • 21 Mustard J. F, Perry D. W, Ardlie N. G, and Packham M. A. 1972; Preparation of suspensions of washed platelets from humans. British Journal of Haematology 22: 193.
    CrossrefPubMedSearch in Google Scholar
  • 22 O’Brien J. R. 1962; Platelet aggregation. I. Some effects of the adenosine phosphates, thrombin and cocaine upon platelet adhesiveness. Journal of Clinical Pathology 15: 446.
    CrossrefPubMedSearch in Google Scholar
  • 23 Packham M. A, Warrior E. S, Glynn M. F, Senyi A. S, and Mustard J. F. 1967; Alteration of the response of platelets to surface stimuli by pyrazole compounds. Journal of Experimental Medicine 126: 171.
    CrossrefPubMedSearch in Google Scholar
  • 24 Parker K. D, Elliott H. W, Wright J. A, Nomof H, and Hine C. H. 1970; Blood and urine concentrations of subjects receiving barbiturates, meprobamate, glutethimide or diphenylhydantoin. Clinical Toxicology 3: 131.
    CrossrefPubMedSearch in Google Scholar
  • 25 Roth S, and Seeman P. 1971; All lipid soluble anesthetics protect red cells. Nature 231: 284.
    PubMedSearch in Google Scholar
  • 26 Roth S, and Seeman P. 1972; The membrane concentrations of neutral and positive anesthetics (alcohols, chlorpromazine, morphine) fit the Meyer-Overton rule of anesthesia; negative narcotics do not. Biochimica et Biophysica Acta 255: 207.
    CrossrefPubMedSearch in Google Scholar
  • 27 Seeman P. 1970. Membrane stabilization and expansion by drugs. In: Deutsch E, Gerlach E, and Moser K. (eds.) Metabolism and Membrane Permeability. Stuttgart; Georg Thieme Verlag,: 384.
    Search in Google Scholar
  • 28 Seeman P, and Roth S. 1972; General anesthetics expand cell membranes at surgical concentrations. Biochimica et Biophysica Acta 255: 171.
    CrossrefPubMedSearch in Google Scholar
  • 29 Thesleff S. 1956; The effect of anesthetic agents on skeletal muscle membrane. Acta Phy-siologica Scandinavia 37: 335.
    CrossrefPubMedSearch in Google Scholar
  • 30 Ueda I. 1971; The effects of volatile general anesthetics on adenosine diphosphate-induced platelet aggregation. Anesthesiology 34: 405.
    CrossrefPubMedSearch in Google Scholar