Reference : Pharmacological characterization of N-tert-butyl-N’-[2-(4’-methylphenylamino)-5-nitroben...
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/23117
Pharmacological characterization of N-tert-butyl-N’-[2-(4’-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time
English
Dogné, Jean-Michel [Université de Liège - ULg > Département de pharmacie > Département de pharmacie >]
Hanson, Julien mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
De leval, X. [> >]
Kolh, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
Tchana-Sato, Vincent [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie cardio-vasculaire >]
de Leval, Laurence mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Département des sciences biomédicales et précliniques >]
Rolin, S. [> >]
Ghuysen, Alexandre mailto [Université de Liège - ULg > Département des sciences de la santé publique > Réanimation - Urgence extrahospitalière >]
Segers, P. [> >]
Lambermont, Bernard mailto [Centre Hospitalier Universitaire de Liège - CHU > > Frais communs médecine >]
Masereel, B. [> >]
Pirotte, Bernard mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
2004
Journal of Pharmacology and Experimental Therapeutics (The)
American Society for Pharmacology and Experimental Therapeutics
309
2
498-505
Yes (verified by ORBi)
International
0022-3565
1521-0103
Bethesda
MD
The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor in rats, and to determine its effects on mice bleeding time. Intraperitoneal injection of a single dose of 5 mg/kg BM-573 to rats inhibited U-46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F-2)-induced washed platelet aggregation 30 min and 1, 2, and 4 h after drug administration with a maximum antiplatelet effect observed after 1 and 2 h. In a rat model of thrombosis induced by ferric chloride application on the abdominal aorta, BM-573 significantly reduced the thrombus weight by 92.53, 80.20, 64.75, and 18.21% at doses of 5, 2, 0.5, and 0.2 mg/kg, respectively. Time to occlusion of abdominal aorta in the BM-573-treated group (41.50+/-5.21 min) was significantly prolonged compared with the vehicle-treated rats (16.16+/-0.79 min). Like furegrelate, seratrodast, and acetylsalicylic acid, BM-573 did not affect the tail bleeding time induced by tail transection in mice compared with vehicle-treated mice. Moreover, BM-573, a close derivative of the loop diuretic torasemide, failed to induce a significant increase in diuresis in rat and did not produce a decrease in blood glucose concentration as observed with the sulfonylurea glibenclamide. In conclusion, we have demonstrated that the nitrobenzenic sulfonylurea BM-573, an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor, is a potent antithrombotic agent that does not affect bleeding time. Moreover, BM-573 lost the diuretic property of torasemide and has no impact on glycemia.
http://hdl.handle.net/2268/23117
10.1124/jpet.103.063610

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