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

• Published in: Haemostasis Vol. 22; no. 6; p. 322
• Main Authors: Giedrojc, J, Fellier, H, Breddin, H K
• Format: Journal Article
• Language: English
• Published: Switzerland 1992
• Subjects: Animals; Aspirin - analogs & derivatives; Aspirin - pharmacology; Drug Synergism; Epoprostenol - analogs & derivatives; Epoprostenol - pharmacology; Fibrinolytic Agents - pharmacology; Heparin, Low-Molecular-Weight - pharmacology; Lasers - adverse effects; Lysine - analogs & derivatives; Lysine - pharmacology; Male; Microcirculation; Molsidomine - pharmacology; Rats; Rats, Wistar; Receptors, Thromboxane - antagonists & inhibitors; Sulfonamides; Thiophenes; Thrombophlebitis - etiology; Thrombophlebitis - prevention & control; Venules - injuries
• ISSN: 0301-0147
• DOI: 10.1159/000216342

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.