Effects of SanOrg123781A, a synthetic hexadecasaccharide, in a mouse model of electrically induced carotid artery injury: synergism with the antiplatelet agent clopidogrel
| Autor: | Régis Masson, Janine Lorrain, Jean-Pascal Herault, Jean-Marc Herbert, Nigel Roome, Paul J. Schaeffer, Stephen E. O'Connor, Christiane Gauffeny, Irène Lechaire |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Ticlopidine Platelet Aggregation medicine.drug_class Low molecular weight heparin Pharmacology Fondaparinux Mice Polysaccharides Antithrombotic Medicine Animals Carotid Artery Thrombosis Aspirin Mice Inbred BALB C business.industry Antagonist Drug Synergism Thrombosis Clopidogrel Electric Injuries Anesthesia Molecular Medicine Platelet aggregation inhibitor business Carotid Artery Injuries Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 309(1) |
| ISSN: | 0022-3565 |
| Popis: | SanOrg123781A is a synthetic hexadecasaccharide that displays antithrombin-dependent inhibition of factor Xa and thrombin and potent antithrombotic effects. The antithrombotic activity of SanOrg123781A has been studied in a new mouse model of arterial thrombosis, where thrombus formation was induced by the application of an electrical current to the adventitial surface of a carotid artery. In this model, antiplatelet agents such as the ADP-receptor antagonist clopidogrel (30 mg/kg, p.o. 2 h before stimulation) and the GpIIb/IIIa antagonist SR121566A [3-(N-[4-(4-[amino(imino)methyl]phenyl)-1,3-thiazol-2-yl]-N-[1-(carboxymethyl)piperidin-4-yl]amino)propionic acid, trihydrochloride] (0.3 mg/kg, i.v. 5 min before stimulation) strongly prolonged the time to occlusion (TTO) (761 and 473% increases, respectively), whereas aspirin was devoid of antithrombotic activity. Standard heparin (2 mg/kg, i.v.), the low molecular weight heparin enoxaparin (20 mg/kg, i.v.), and the synthetic, antithrombin-dependent inhibitor of factor Xa fondaparinux (10 mg/kg, i.v.) were also active in this model (742, 707, and 602% TTO increases, respectively). Interestingly, SanOrg123781A was active at much lower doses than the other oligosaccharides (554% increase in TTO at 0.3 mg/kg, i.v. 5 min before stimulation). Low doses of SanOrg123781A administered in combination with low doses of clopidogrel led to a marked increase in TTO, which was statistically more important than the additive effects of the two compounds given alone. These results indicate that SanOrg123781A exerts a potent antithrombotic activity in a mouse model of arterial thrombosis when compared with reference compounds and show that the combination of SanOrg123781A with clopidogrel leads to a marked synergistic antithrombotic effect. |
| Databáze: | OpenAIRE |
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