Agents and Actions

, Volume 36, Supplement 2, pp C434–C436 | Cite as

The antihistamine drug cimetidine and arachidonic acid metabolism

  • V. Jančinová
  • M. Petríková
  • R. Nosál
Plenary Lecture Histamine Receptors, Antihistamines and Clinical Studies
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Abstract

Results of our previous study showed that the antihistamine drug cimetidine inhibited functions of blood platelets. The aim of the present paper was to analyse in detail the mechanism of this action. We focussed our attention on the effect of cimetidine on three steps of arachidonic acid metabolism-liberation of arachidonate, biosynthesis of thromboxane A2 and malondialdehyde formation.

Cimetidine in the concentration range from 0.01 to 1 mmol/l did not inhibit either thrombin-stimulated liberation of3H-arachidonic acid from individual platelet phospholipids nor malondialdehyde production. Cimetidine at the concentration of 1 mmol/l, however, significantly inhibited the production of thromboxane B2, the stable metabolite of TXA2.

Cimetidine appears to inhibit platelet functions by inhibiting arachidonic acid metabolism at the step of conversion of cyclic endoperoxides, PGG2 and PGH2, to thromboxane A2.

Keywords

Arachidonic Acid Cimetidine Acid Metabolism Malondialdehyde Thromboxane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. [1]
    W. O. Richter, W. Rollinghoff, R. Lamerz and P. Schwandt,Thrombozytopenie durch Cimetidin. Deutsche Medizinische Wochenschrift108, 558–559 (1983).Google Scholar
  2. [2]
    V. Jančinová and R. Nosál,Cimetidine and ketotifen inhibit stimulated aggregation and histamine liberation from rabbit blood platelets. Agents and Actions27, 135–137 (1989).PubMedGoogle Scholar
  3. [3]
    B. Gachályi, K. Tihanyi, Á. Vas and A. Káldor,In vitro effect of cimetidine on ADP induced platelet aggregation and thromboxane A 2 synthesis in man. Thromb. Res.35, 105–109 (1984).CrossRefPubMedGoogle Scholar
  4. [4]
    T. Tomita, K. Umegaki, K. Nakamura and E. Hayashi,Impaired function of TX A 2 and/or calcium in the platelets from SHRSP at hypertensive ages. Thromb. Res.35, 219–230 (1984).CrossRefPubMedGoogle Scholar
  5. [5]
    V. Jančinová and R. Nosál,Differences among betaadrenoceptor blocking drugs in modifying platelet aggregation and arachidonic acid liberation under thrombin stimulation. Thromb. Res.54, 687–698 (1989).CrossRefPubMedGoogle Scholar
  6. [6]
    R. M. McMillan, D. E. MacIntyre and J. L. Gordon,Simple, sensitive fluorimetric assay for malondialdehyde production by blood platelets. Thromb. Res.11, 425–428 (1977).CrossRefPubMedGoogle Scholar
  7. [7]
    H. Ohkawa, N. Ohishi and K. Yagi,Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem.95, 351–358 (1979).CrossRefPubMedGoogle Scholar
  8. [8]
    G. Allan, K. E. Eakins, P. S. Kulkarni and R. Levi,Inhibition of thromboxane A 2 biosynthesis in human platelets by burimamide. Br. J. Pharmac.71, 157–164 (1980).Google Scholar
  9. [9]
    K. Fredriksson, I. Rosén, B. B. Johansson and T. Wieloch,Cerebral platelet thromboembolism and thromboxane synthetase inhibition. Stroke16, 800–805 (1985).PubMedGoogle Scholar
  10. [10]
    D. P. Mikhailidis, M. A. Barradas, J. Y. Jeremy and P. Dandona,In vitro effect of cimetidine on platelet aggregation. Thromb. Res.38, 307–308 (1985).CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1992

Authors and Affiliations

  • V. Jančinová
    • 1
  • M. Petríková
    • 1
  • R. Nosál
    • 1
  1. 1.Institute of Experimental PharmacologySlovak Academy of SciencesBratislavaCzecho-Slovakia

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