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Thromb Haemost 1981; 45(02): 158-161
DOI: 10.1055/s-0038-1650155
Original Article
Schattauer GmbH Stuttgart

Inhibition of Human Platelet Functions by Verapamil

Y Ikeda
The Department of Hematology, Keio University, School of Medicine, Tokyo, Japan
,
M Kikuchi
The Department of Hematology, Keio University, School of Medicine, Tokyo, Japan
,
K Toyama
The Department of Hematology, Keio University, School of Medicine, Tokyo, Japan
,
K Watanabe
*   Department of Clinical Pathology, Keio University, School of Medicine, Tokyo, Japan
,
Y Ando
*   Department of Clinical Pathology, Keio University, School of Medicine, Tokyo, Japan
› Institutsangaben
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Publikationsverlauf

Received 02. April 1980

Accepted after revision 05. Februar 1981

Publikationsdatum:
05. Juli 2018 (online)

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Summary

The effects of verapamil, a coronary vasodilator, on platelet functions were studied.

Platelet aggregation induced by ADP, epinephrine or collagen was inhibited by verapamil in vitro. Calcium ionophore A23187-induced platelet aggregation was also inhibited by verapamil in a concentration dependent manner. In washed platelets, verapamil caused a dose-dependent inhibition of serotonin release induced either by thrombin or A23187 in the absence of extracellular calcium. Addition of 1 mM CaCl2 with A23187 or thrombin partially overcame this inhibition. Addition of 1 mM CaCl2 in the absence of verapamil had no effect on thrombin- or A23187-induced secretion. When verapamil was administered to the healthy volunteers at the dosage commonly used, inhibition of platelet aggregation was observed 2 hrs after the drug ingestion. It is of great interest that verapamil potentiated the anti-aggregating activity of prostacyclin in vitro.

Our results may suggest a potential role for verapamil in the treatment of thrombotic disorders.

Keywords

Verapamil - Calcium antagonist - Platelet function - Anti-platelet agent
 

  • References

  • 1 Carvalho ACA, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290: 434-438
    CrossrefPubMedGoogle Scholar
  • 2 Wu KK. Platelet hyperaggregability and thrombosis in patients with thrombocythemia. Ann Intern Med 1978; 88: 7-11
    CrossrefPubMedGoogle Scholar
  • 3 Wu KK, Hoak JC. Spontaneous platelet aggregation in arterial insufficiency: Mechanism and implications. Thromb Haemostas 1976; 35: 702-706
    PubMedGoogle Scholar
  • 4 Moncada S, Higgs EA, Vane JR. Human arterial and venous tissues generate prostacyclin, a potent inhibitor of platelet aggregation. Lancet 1977; 01: 18-20
    PubMedGoogle Scholar
  • 5 Haas H, Haetfelder G. α-Isopropyl-α-[(N-methyl-N-homoveratryl)-γ-amino-propyl]-3,4-dimethoxyphenylocetonitril, eine Substanz mit koronargefäßerweiternden Eigenschaften. Arzneim Forsch 1962; 12: 549-552
    PubMedGoogle Scholar
  • 6 Haeusler G. Differential effect of verapamil on excitation-contraction coupling in smooth muscle and on excitation-secretion coupling in adrenergic nerve terminals. J Pharmacol Exp Ther 1972; 180: 672-682
    PubMedGoogle Scholar
  • 7 Stormorken H. The release reaction of secretion. Scand J Haematol. 1969. Suppl, 9-23
    Google Scholar
  • 8 Feinman RD, Detwiler TC. Platelet secretion induced by divalent cation ionophores. Nature 1974; 249: 172
    CrossrefPubMedGoogle Scholar
  • 9 White JG, Rao GHR, Gerrard JM. Effect of the ionophore A23187 on blood platelets. Amer J Path 1974; 77: 135-149
    PubMedGoogle Scholar
  • 10 Born G VR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 937
    PubMedGoogle Scholar
  • 11 Mills DCB, Roft IA, Roberts G CK. The release of nucleotides, 5-hydroxytryptamine and enzyme from human blood platelets during aggregation. J Physiol 1968; 195: 715-729
    CrossrefPubMedGoogle Scholar
  • 12 Rasmussen H. Cell communication, calcium ion and cyclic adenosine monophosphate. Science 1970; 197: 1970
    PubMedGoogle Scholar
  • 13 Murer EH, Stewart GL, Rausch MA, Day HJ. Calcium ionophore A23187. Thrombos Diathes Hemorrh 1975; 34: 72-82
    PubMedGoogle Scholar
  • 14 Charo IF, Feinman RD, Detwiler TC. Inhibition of platelet secretion by an antagonist of intracellular calcium. Biochem Biophys Res Commun 1976; 72: 1462-1467
    CrossrefPubMedGoogle Scholar
  • 15 Schomerus M, Spiegelhalder B, Stieren B, Eichelbaum K. Physiological disposition of verapamil in man. Cardiovas Res 1976; 10: 605-612
    CrossrefPubMedGoogle Scholar
  • 16 Ikeda Y, Kikuchi M, Watanabe K, Ando Y. Inhibition of platelet functions by sulbenicillin and its metabolite. Antimicrob Agents Chemother 1978; 13: 881-883
    CrossrefPubMedGoogle Scholar
  • 17 Hamberg M, Svensson J, Wakabayashi T, Samuelson B. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci USA 1974; 71: 345-349
    CrossrefPubMedGoogle Scholar
  • 18 Hamberg M, Samuelson B. Prostaglandin endoperoxides. Novel transformation of arachidonic acid in human platelets. Proc Natl Acad Sci USA 1974; 71: 3400-3404
    CrossrefPubMedGoogle Scholar
  • 19 Malmsten C, Hamberg M, Svensson J, Samuelson B. Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency. Proc Natl Acad Sci USA 1975; 72: 1446-1450
    CrossrefPubMedGoogle Scholar
  • 20 Moncada S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibitis platelet aggregation. Nature 1976; 263: 663-665
    CrossrefPubMedGoogle Scholar
  • 21 Hirsh J. Clinical effects of platelet function suppressing drugs. In “Platelets and thrombosis”. Mills DC B, and Pareti FI. eds 1975. pp 175-182 Academic Press; London:
    Google Scholar