Abstract
The pharmacomodulation of sulfonylureas structurally related to torasemide and characterized by a TXA(2)antagonism led to the synthesis of BM-573. This original molecule showed a high affinity (IC(50)1.3 nM) for the TXA(2)receptor of human platelets in comparison with both reference compounds, SQ-29548 (IC(50)21 nM) and sulotroban (IC(50)930 nM). Moreover, this torasemide derivative was found to be a potent inhibitor of human platelet aggregation induced by arachidonic acid (ED(100)=0.13 microM) or by U-46619 (ED(50)=0.24 microM), a TXA(2)agonist. BM-573 relaxed the isolated rat thoracic aorta (ED(50)=28.4 nM) and guinea-pig trachea (ED(50)=17.7 nM) contracted by U-46619. BM-573 (1 microM) completely reduced the platelet production of TXB(2)induced by arachidonic acid. Finally, BM-573 (30 mg/kg, per os) lost the diuretic properties of torasemide in rats.
Original language | English |
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Pages (from-to) | 67-72 |
Number of pages | 6 |
Journal | Prostaglandins, Leukotrienes and Essential Fatty Acids |
Volume | 65 |
Issue number | 2 |
DOIs | |
Publication status | Published - Aug 2001 |
Keywords
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
- Animals
- Antihypertensive Agents
- Aorta
- Arachidonic Acid
- Blood Platelets
- Dose-Response Relationship, Drug
- Guinea Pigs
- Humans
- Hydrazines
- Inhibitory Concentration 50
- Models, Chemical
- Muscle, Smooth
- Platelet Aggregation
- Platelet Aggregation Inhibitors
- Rats
- Rats, Wistar
- Receptors, Thromboxane
- Sulfonamides
- Thromboxane-A Synthase
- Trachea
- Vasoconstrictor Agents