Pharmacology of the Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor BM-531 Jean-Michel Dogné, Stéphanie Rolin, 1 Xavier de Leval, Patricia Benoit, Philippe Neven, Jacques Delarge, Philippe Kolh, 2 Jacques Damas, 3 Jean-Louis David, 4 and Bernard Masereel 1 University of Liège, Department of Medicinal Chemistry, 2 Department of Cardiac Surgery, 3 Department of Human Physiology, and 4 Department of Thrombosis and Hemostasis, Liège, Belgium 1 Universityof Namur, Department of Pharmacology, Namur, Belgium Key Words: Antiplatelet agents—BM-531—Sulfonylurea—Thromboxane an- tagonist—Thromboxane synthase inhibitor. ABSTRACT BM-531 (N-tert-butyl-N¢ -[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a tora- semide derivative, is a novel noncarboxylic thromboxane receptor antagonist and throm- boxane synthase inhibitor. Indeed, its affinity for human washed platelet TXA 2 receptors labeled with [ 3 H]SQ-29548 (IC 50 = 0.0078 mM) is higher than sulotroban (IC 50 = 0.93 mM) and SQ-29548 (IC 50 = 0.021 mM). Moreover, BM-531 is characterized by a potent antiaggregatory property. Indeed, on one hand, in human citrated platelet-rich plasma BM-531 prevents platelet aggregation induced by arachidonic acid (600 mM) (ED 100 = 0.125 mM), U-46619, a stable TXA 2 agonist (1 mM) (ED 50 = 0.482 mM) or collagen (1 mg/ mL) (percentage of inhibition: 42.9% at 10 mM) and inhibits the second wave of ADP (2 mM)-induced aggregation. On the other hand, when BM-531 is incubated in whole blood from healthy donors, the closure time measured by the recently developed platelet function analyser (PFA-100 ® ) is significantly prolonged. In addition, at the con- centrations of 10 and 1 m M, BM-531 totally prevents the production of TXB 2 by human platelets activated by arachidonic acid. Finally, at 10 mM, BM-531 significantly prevents rat fundus contractions induced by U-46619 but not by prostacyclin. These results suggest that BM-531, which is devoid of the diuretic property of torasemide, can be regarded as a promising antiplatelet agent. 87 Cardiovascular Drug Reviews Vol. 19, No. 2, pp. 87–96 © 2001 Neva Press, Branford, Connecticut Address correspondence and reprint requests to: Jean-Michel Dogné, University of Liège, Institute of Pharmacy, Department of Medicinal Chemistry, 1, avenue de l’Hôpital, tour 4, +5, Bât. B36 B-4000 Liège, Belgium. Phone: +32 (4) 366-4382. Fax: +32 (4) 366-4362. E-mail: Jean-Michel.Dogne@ulg.ac.be.