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Effects of a novel non-carboxylic thromboxane A2 receptor antagonist (BM-531) derived from torasemide on platelet function

Authors
Journal
Prostaglandins Leukotrienes and Essential Fatty Acids (PLEFA)
0952-3278
Publisher
Elsevier
Publication Date
Volume
62
Issue
5
Identifiers
DOI: 10.1054/plef.2000.0160

Abstract

Abstract In this study we examined the thromboxane A 2(TXA 2) receptor antagonist property of BM-531 ( N-tert -butyl- N′-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative, on platelet function. The drug affinity for human washed platelet TXA 2receptors labelled with [ 3H]SQ-29,548 has been determined (IC50: 0.0078 μM) and demonstrated to be higher than sulotroban (IC50: 0.93 μM) and SQ-29,548 (IC50: 0.021 μM). The antiaggregatory potency has been confirmed since we demonstrated that BM-531 prevented platelet aggregation in human citrated platelet-rich plasma induced by arachidonic acid (600 μM) (ED100: 0.125 μM), U-46619, a stable TXA 2agonist (1 μM) (ED50: 0.482 μM) and collagen (1 μg mL −1) (% of inhibition: 42.9% at 10 μM) and inhibited the second wave of ADP (2 μM). Moreover, when BM-531 was incubated in whole blood from healthy donors, the closure time measured by the recently developed platelet function analyser (PFA-100 ™) was significantly prolonged. These results suggest that BM-531 can be regarded as a novel non-carboxylic TXA 2antagonist with a powerful antiplatelet potency.

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