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Individual and combined effects of a thromboxane receptor antagonist and different antithrombotic agents in a rat microcirculatory thrombosis model.

Abstract
The antithrombotic effect of a thromboxane A2 receptor antagonist (HN-11501:5-[2-(4-chlorophenylsulfonylamino)-ethyl]-2-thienylox y-acetic acid) alone and in combination with other antithrombotic agents has been studied in an experimental thrombosis model in which laser lesions are used to induce a defined thrombosis in rat mesenteric venules. The thromboxane receptor antagonist showed a significant and dose-dependent antithrombotic effect if given orally. The strongest additive thrombosis-inhibiting effect was observed after oral administration of HN-11501 at a dose of 2.5 mg/kg together with an intravenous infusion of 1 microgram/kg/h of a prostacyclin analogue (cicaprost). An additive antithrombotic effect was also observed after oral application of 2.5 mg/kg of HN-11501 and intravenous injection of 0.2 mg/kg of a low molecular weight heparin (Fraxiparine). The combination of 2.5 mg/kg of HN-11501 orally with an intravenous injection of 0.1 mg/kg molsidomine also had a significant additive effect. No significant additive effect was observed when 2.5 mg/kg of HN-11501 and 10 mg/kg of acetylsalicylic acid were orally administered simultaneously.
AuthorsJ Giedrojc, H Fellier, H K Breddin
JournalHaemostasis (Haemostasis) Vol. 22 Issue 6 Pg. 322-9 ( 1992) ISSN: 0301-0147 [Print] Switzerland
PMID1335951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Receptors, Thromboxane
  • Sulfonamides
  • Thiophenes
  • HN 11501
  • Molsidomine
  • Epoprostenol
  • Lysine
  • cicaprost
  • Aspirin
  • acetylsalicylic acid lysinate
Topics
  • Animals
  • Aspirin (analogs & derivatives, pharmacology)
  • Drug Synergism
  • Epoprostenol (analogs & derivatives, pharmacology)
  • Fibrinolytic Agents (pharmacology)
  • Heparin, Low-Molecular-Weight (pharmacology)
  • Lasers (adverse effects)
  • Lysine (analogs & derivatives, pharmacology)
  • Male
  • Microcirculation
  • Molsidomine (pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Thromboxane (antagonists & inhibitors)
  • Sulfonamides
  • Thiophenes
  • Thrombophlebitis (etiology, prevention & control)
  • Venules (injuries)

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