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2004 | 51 | 1 |

Tytuł artykułu

The effect of some epsilon-aminocaproic acid derivatives on platelet responses

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
ε-Aminocaproic acid (EACA) is a synthetic low molecular drug with antifibrinolytic activity. However, treatment with this drug can be incidentally associated with an in­creased thrombotic tendency. The aim of the present work was to test synthetic EACA derivatives for their antiplatelet activities. We investigated the effect of three EACA derivatives with antifibrinolytic activity: I. ε-aminocaproyl-L-leucine hydro­chloride (HCl*H-EACA-L-Leu-OH), II. ε-aminocaproyl-L-(S-benzyl)-cysteine hydrochlo­ride (HCl*H-EACA-L-Cys(S-Bzl)-OH) and III. ε-aminocaproyl-L-norleucine (H-EACA-L-Nle-OH) on platelet responses (aggregation and adhesion) and on their in­tegrity. It was found that: 1. as judged by LDH release test, none of the tested com­pounds, up to 20 mM, was toxic to platelets, 2. in comparison with EACA, all the syn­thetic derivatives inhibited much stronger the ADP- and collagen-induced aggrega­tion of platelets suspended in plasma (platelet rich plasma) and aggregation of these cells in whole blood, 3. EACA and its derivatives exerted a similar inhibitory effect on the thrombin-induced adhesion of platelets to fibrinogen-coated surfaces. Since platelet activation and blood coagulation are tightly associated processes, the antiplatelet properties of EACA derivatives are expected to indicate reduced throm- botic properties of these derivatives compared to EACA.

Wydawca

-

Rocznik

Tom

51

Numer

1

Opis fizyczny

p.73-80,fig.,ref.

Twórcy

autor
  • Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland
autor
autor

Bibliografia

  • Barrons RW, Jahr JS. (1996) A review of post-cardiopulmonary bypass bleeding, aminocaproic acid, tranexamic acid, and aprotinin. Am J Ther.; 3: 821-38.
  • Bellavite P, Andrioli G, Guzzo P, Chirumbolo S, Manzato F, Santonastaso C. (1994) A colorimetric method for the measurement of platelet adhesion in microtiter plates. Anal Biochem.; 216: 444-50.
  • Bergmeyer HU, Bernt E, Hess B. (1965) Lactate dehydrogenase. In Methods of Enzymatic Analysis. Bergmeyer HU, ed, p 736. Academic Press Inc., New York.
  • Born GVR. (1963) Quantitative investigation into aggregation of blood platelets. J Physiol.; 168: 178-95.
  • Cardinal DC, Fower RJ. (1980) The electronic aggregometer: a novel device for assessing platelet behavior in blood. J Farmacol Methods.; 3: 135-43. Chrono-Log Corp. (1987)
  • Manual for Testing with the Whole-blood Aggregometer Model 550. Havertown, PA.
  • DelRossi AJ, Cernainau AC, Botros S, Lemole GM, Moore R. (1989) Prophylactic treatment of postperfusion bleeding using EACA. Chest.; 96: 27-30.
  • Dunn CJ, Goa KL. (1999) Tranexamic acid. A review of its use in surgery and other indications. Drugs.; 57: 1005-32.
  • Green D, Ts'ao CH, Cerullo L, Cohen I, Ruo TI, Atkinson AJ. (1985) Clinical and laboratory investigation of the effects of epsilon-aminocaproic acid on hemostasis. J Lab Clin Med.; 105: 321-7.
  • Hardy J. (1992) Natural and synthetic antifibrinolytics in cardiac surgery. Can JAnaesth.; 39: 353-65.
  • Heemskerk J, Bevers E, Lindhout T. (2002) Platelet activation and blood coagulation. Thromb Haemost.; 88: 186-93.
  • Maciejewska D, Midura-Nowaczek K, Wawer I. (2002) Conformational analysis of epsilon-aminocaproyl-alpha- aminoacids in solution and solid state by 1H, 13C NMR spectroscopy and molecular modeling. J Mol Struct.; 604: 269-78.
  • Mannucci PM. (1998) Hemostatic drugs. N Engl J Med.; 339: 245-53.
  • Markwardt F. (1978) Fibrinolytics and antifibrinolytics. In Handbook of Experimental Pharmacology vol 46. Springer, Berlin, Heidelberg, New York.
  • Midura-Nowaczek K, Bruzgo I, Dubis E, Roszkowska-Jakimiec W, Worowski K. (1996) Antifibrinolytic activity of epsilon-aminocaproyl derivatives of amino acids. Pharmazie.; 51: 775-7.
  • Midura-Nowaczek K, Bruzgo I, Poplawski J, Roszkowska-Jakimiec W, Worowski K. (1998) Effects of epsilon- aminocaproylaminoacids on fibrynolytic and caseinolytic activity of euglobulin fraction. Acta Pol Pharm.; 55: 159-61.
  • Monroe DM, Hoffman M, Roberts HR. (2002) Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. ; 22: 1381-9.
  • Munoz JJ, Birkmeyer NJO, Birkmeyer JD, O'Connor GTO, Dacey LJ. (1999) Is epsilon-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery? A meta-analysis. Circulation.; 99: 81-9.
  • Peters DC, Noble S. (1999) Aprotinin. An update of its pharmacology and therapeutic use in open heart surgery and coronary bypass surgery. Drugs.; 57: 233-60.
  • Porte RJ, Leebeek FWG. (2002) Pharmacological strategies to decrease transfusion requirements in patients undergoing surgery. Drugs.; 62: 2193-211.
  • Verstraete M. (1985) Clinical application of inhibitors of fibrinolysis. Drugs.; 29: 236-61.

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Bibliografia

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