[en] The aim of this work was to evaluate the effects of BM-567 ( N-pentyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative. on both thromboxane A(2) (TXA(2)) receptors (TP) and thromboxane synthase of human platelets. The drug affinity for TP receptors of human washed platelets has been determined. In this test BM-567 showed a high affinity (IC50: 1.1+/-0.1 nM) for the TP receptors in comparison with BM-531 (IC50: 7.8+/-0.7 nM) and sulotroban (IC50: 931+/-85 nM), two TXA(2) antagonists. We also demonstrated that BM-567 prevented platelet aggregation induced by arachidonic acid (AA) (600 muM) (ED100: 0.20+/-0.10muM), U-46619, a stable TXA(2) agonist (1 muM) (ED50: 0.30+/-0.04 muM) and collagen (1 mug ml(-1)) (% of inhibition: 44.3+/-4.3% at 10 muM) and inhibited the second wave of ADP (2 muM). Moreover, when BM-567 was incubated in whole blood from healthy donors, the closure time measured by the Platelet Function analyzer (PFA-100) was significantly prolonged (closure time: 215+/-21 s) by using collagen/epinephrine cartridges. Finally, at the concentration of 1 muM, BM-567 completely reduced the TXB2 production from human platelets stimulated with AA (600 muM). These results indicate that BM-567 is a novel combined TXA(2) receptor antagonist and thromboxane synthase inhibitor characterized by a powerful antiplatelet potency. (C) 2002 Elsevier Science Ltd. All rights reserved.
Dogné, Jean-Michel ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
de Leval, X.; Université de Liège - ULiège > Département de chimie médicale > Laboratoire de chimie médicale
Kolh, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Service de biochimie et de physiologie humaines, normale et pathologique
Sanna, V.; Université de Liège - ULiège > Département de chimie médicale > Laboratoire de chimie médicale
Rolin, Stéphanie; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Département de Pharmacie
Michaux, C.; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Laboratoire chimie molécullaire structurelle
Mauer, M.; Centre Hospitalier Universitaire de Liège - CHU > Département de biostatistique
David, Jean-Louis ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Masereel, B.; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Département de Pharmacie
Pirotte, Bernard ; Université de Liège - ULiège > Chimie pharmaceutique
Language :
English
Title :
Pharmacological evaluation of the novel thromboxane modulator BM-567 (I/II). Effects of BM-567 on platelet function
Publication date :
January 2003
Journal title :
Prostaglandins, Leukotrienes, and Essential Fatty Acids
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