Torasemide, a loop diuretic, has been reported to relax dog coronary artery precontracted by thromboxane A2 (TXA2), an endogenous prostanoid involved in cardiovascular and pulmonary diseases. N-cyano-N'-[[4-(3'-methylphenylamino)pyrid-3-yl]sulphonyl] homopiperidinoamidine (BM-144) and N-isopropyl-N'-[5-nitro-2-(3'-methylphenylamino)-benzenesulphon yl]urea (BM-500), chemically related to torasemide, have been examined for their TXA2 antagonism. The affinity (IC50, the concentration resulting in 50% inhibition) of BM-144 and BM-500 for the TXA2 receptor of washed platelets from man was 0.28 and 0.079 microM, respectively. This is better than for sulotroban (IC50 = 0.93 microM) but less than for SQ-29548 (IC50 = 0.021 microM), two TXA2 antagonists used as reference. The aggregation of platelets from man induced by arachidonic acid was prevented by BM-144 (IC50 = 9.0 microM) and by BM-500 (IC50 = 14.2 microM). Similar results were obtained by use of U-46619, a TXA agonist, as aggregating agent (BM-144, IC50 = 12.9 microM and BM-500, IC50 = 9.9 microM). The contracting effect of U-46619 on rat stomach strip was abolished by BM-144 (IC50 = 1.01 microM) and BM-500 (IC50 = 2.54 microM). Both drugs (BM-144: IC50 = 0.12 microM and BM-500: IC50 = 0.19 microM) also relaxed rat aorta precontracted by U-46619; both were more potent than sulotroban (IC50 = 1.62 microM). The two torasemide derivatives (100 microM) did not significantly affect the myo-stimulating effect of some prostaglandins (PGE2, PGI2, PGF2alpha) or aorta contraction elicited by KCl (30 mM). They did not modify rat diuresis after administration of a 30-mg kg(-1) dose. In conclusion, BM-144 and BM-500 can be regarded as novel non-carboxylic TXA2 receptor antagonists and offer a novel template for the design of more potent molecules.