Effects of a novel non-carboxylic thromboxane A(2) receptor antagonist (BM-531) derived from torasemide on platelet function

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)sul fonl]urea), a torasemide derivative, on platelet function. The drug affinit y for human washed platelet TXA(2) receptors labelled with [H-3]SQ-29,548 h as been determined (IC50: 0.0078 mu M) and demonstrated to be higher than s ulotroban (IC50: 0.93 mu M) and SQ-29,548 (IC50: 0.021 mu M). The antiaggre gatory potency has been confirmed since we demonstrated that BM-531 prevent ed platelet aggregation in human citrated platelet-rich plasma induced by a rachidonic acid (600 mu M) (ED100: 0.125 mu M), U-46619, a stable TXA(2) ag onist (1 mu M) (ED50: 0.482 mu M) and collagen (1 mu g ml(-1)) (% of inhibi tion: 42.9% at 10 mu M) and inhibited the second wave of ADP (2 mu M). More over, when BM-531 was incubated in whole blood from healthy donors, the clo sure time measured by the recently developed platelet function analyser (PF A-100(R)) was significantly prolonged. These results suggest that BM-531 ca n be regarded as a novel non-carboxylic TXA(2) antagonist with a powerful a ntiplatelet potency. (C) 2000 Harcourt Publishers Ltd.