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.

Détails

ID Serval
serval:BIB_06306705A69D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Journal of Pharmacology and Experimental Therapeutics
Auteur(s)
Dogné J.M., Hanson J., de Leval X., Kolh P., Tchana-Sato V., de Leval L., Rolin S., Ghuysen A., Segers P., Lambermont B., Masereel B., Pirotte B.
ISSN
0022-3565[print], 0022-3565[linking]
Statut éditorial
Publié
Date de publication
2004
Volume
309
Numéro
2
Pages
498-505
Langue
anglais
Résumé
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.
Mots-clé
Animals, Bleeding Time, Blood Glucose/drug effects, Diuretics/pharmacology, Diuretics/therapeutic use, Male, Mice, Platelet Aggregation/drug effects, Rats, Rats, Sprague-Dawley, Receptors, Thromboxane A2, Prostaglandin H2/antagonists & inhibitors, Sulfonylurea Compounds/pharmacology, Sulfonylurea Compounds/therapeutic use, Thrombosis/blood, Thrombosis/drug therapy, Thromboxane-A Synthase/antagonists & inhibitors
Pubmed
Création de la notice
28/10/2010 9:52
Dernière modification de la notice
20/08/2019 12:28
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