ISSN:
1527-3466
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
BM-531 (N-tert-butyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative, is a novel noncarboxylic thromboxane receptor antagonist and thromboxane synthase inhibitor. Indeed, its affinity for human washed platelet TXA2 receptors labeled with [3H]SQ-29548 (IC50= 0.0078 μM) is higher than sulotroban (IC50= 0.93 μM) and SQ-29548 (IC50= 0.021 μM). 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 μM) (ED100= 0.125 μM), U-46619, a stable TXA2 agonist (1 μM) (ED50= 0.482 μM) or collagen (1 μg/mL) (percentage of inhibition: 42.9% at 10 μM) and inhibits the second wave of ADP (2 μM)-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 concentrations of 10 and 1 μM, BM-531 totally prevents the production of TXB2 by human platelets activated by arachidonic acid. Finally, at 10 μM, 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1527-3466.2001.tb00057.x
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