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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1972 May;25(5):427–432. doi: 10.1136/jcp.25.5.427

Effect in vitro on platelet function of two compounds developed from the pyrimido-pyrimidines

S D Slater 1, A G G Turpie 1, A S Douglas 1, G P McNicol 1
PMCID: PMC477339  PMID: 5046075

Abstract

VK 774 and VK 744, two new compounds developed from the pyrimido-pyrimidines, have been found to be powerful inhibitors of platelet function tested in vitro. They inhibit adenosine diphosphate (ADP)-induced platelet aggregation, and the release of platelet factor 3 by kaolin, and VK 774 also reduces platelet adhesiveness and inhibits platelet aggregation (`snowstorm' effect) in the Chandler tube system. Although measured percentage whole blood clot retraction was uninfluenced by these drugs the clot produced with VK 774 was friable and soft. VK 774 appears to be the most powerful of these compounds reported so far, being active in some test systems at 10−6M, and, if the results of toxicity testing are satisfactory, it should be an important agent for therapeutic trial.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CHANDLER A. B. In vitro thrombotic coagulation of the blood; a method for producing a thrombus. Lab Invest. 1958 Mar-Apr;7(2):110–114. [PubMed] [Google Scholar]
  2. CUNNINGHAM G. M., MCNICOL G. P., DOUGLAS A. S. EFFECT OF ANTICOAGULANT DRUGS ON PLATELET AGGREGATION IN THE CHANDLER'S TUBE. Lancet. 1965 Apr 3;1(7388):729–730. doi: 10.1016/s0140-6736(65)92089-1. [DOI] [PubMed] [Google Scholar]
  3. Didisheim P. Inhibition by dipyridamole of arterial thrombosis in rats. Thromb Diath Haemorrh. 1968 Nov 15;20(1):257–266. [PubMed] [Google Scholar]
  4. Elkeles R. S., Hampton J. R., Honour A. J., Mitchell J. R., Prichard J. S. Effect of a pyrimido-pyrimidine compound on platelet behaviour in vitro and in vivo. Lancet. 1968 Oct 5;2(7571):751–754. doi: 10.1016/s0140-6736(68)90952-5. [DOI] [PubMed] [Google Scholar]
  5. Emmons P. R., Harrison M. J., Honour A. J., Mitchell J. R. Effect of dipyridamole on human platelet behaviour. Lancet. 1965 Sep 25;2(7413):603–606. doi: 10.1016/s0140-6736(65)90515-5. [DOI] [PubMed] [Google Scholar]
  6. Forbes C. D., McNicol G. P., Douglas A. S. Action of a pyrimido-pyrimidine compound on platelet behaviour in vitro. Br Med J. 1969 May 24;2(5655):483–485. doi: 10.1136/bmj.2.5655.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gray G. R., Wilson P. A., Douglas A. S. The effect on dipyridamole on platelet aggregation and adhesiveness. Scott Med J. 1968 Dec;13(12):409–415. doi: 10.1177/003693306801301202. [DOI] [PubMed] [Google Scholar]
  8. Hardisty R. M., Hutton R. A. Platelet aggregation and the availability of platelet factor 3. Br J Haematol. 1966 Nov;12(6):764–776. doi: 10.1111/j.1365-2141.1966.tb00164.x. [DOI] [PubMed] [Google Scholar]
  9. Harker L. A., Slichter S. J. Studies of platelet and fibrinogen kinetics in patients with prosthetic heart valves. N Engl J Med. 1970 Dec 10;283(24):1302–1305. doi: 10.1056/NEJM197012102832402. [DOI] [PubMed] [Google Scholar]
  10. Hassanein A. A., Turpie A. G., McNicol G. P., Douglas A. S. Effect of RA233 on platelet function in vitro. Br Med J. 1970 Apr 11;2(5701):83–86. doi: 10.1136/bmj.2.5701.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirsh J., McBride J. A., Dacie J. V. Thrombo-embolism and increased platelet adhesiveness in post-splenectomy thrombocytosis. Australas Ann Med. 1966 May;15(2):122–128. doi: 10.1111/imj.1966.15.2.122. [DOI] [PubMed] [Google Scholar]
  12. MUSTARD J. F., HEGARDT B., ROWSELL H. C., MACMILLAN R. L. EFFECT OF ADENOSINE NUCLEOTIDES ON PLATELET AGGREGATION AND CLOTTING TIME. J Lab Clin Med. 1964 Oct;64:548–559. [PubMed] [Google Scholar]
  13. MUSTARD J. F., MURPHY E. A., ROWSELL H. C., DOWNIE H. G. Factors influencing thrombus formation in vivo. Am J Med. 1962 Nov;33:621–647. doi: 10.1016/0002-9343(62)90243-7. [DOI] [PubMed] [Google Scholar]
  14. Mustard J. F., Packham M. A. Factors influencing platelet function: adhesion, release, and aggregation. Pharmacol Rev. 1970 Jun;22(2):97–187. [PubMed] [Google Scholar]
  15. Mustard J. F., Packham M. A. Thromboembolism: a manifestation of the response of blood to injury. Circulation. 1970 Jul;42(1):1–21. doi: 10.1161/01.cir.42.1.1. [DOI] [PubMed] [Google Scholar]
  16. SPAET T. H., CINTRON J. STUDIES ON PLATELET FACTOR-3 AVAILABILITY. Br J Haematol. 1965 May;11:269–275. doi: 10.1111/j.1365-2141.1965.tb06587.x. [DOI] [PubMed] [Google Scholar]

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