Individual and combined effects of a thromboxane receptor antagonist and different antithrombotic agents in a rat microcirculatory thrombosis model.
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.
Giedrojc
J
J
Department of Internal Medicine, J.W. Goethe University, Frankfurt am Main, FRG.
Fellier
H
H
Breddin
H K
HK
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D007834:Lasers / Q000009:adverse effects; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008833:Microcirculation; D008981:Molsidomine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013449:Sulfonamides; D013876:Thiophenes; D013924:Thrombophlebitis / Q000209:etiology / Q000517:prevention & control*; D014699:Venules / Q000293:injuries
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013876:Thiophenes; C079182:HN 11501; D008981:Molsidomine; D011464:Epoprostenol; D008239:Lysine; C043867:cicaprost; D001241:Aspirin; C010395:acetylsalicylic acid lysinate