Activity of a novel dual thromboxane A(2)receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles

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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 languageEnglish
Pages (from-to)67-72
Number of pages6
JournalProstaglandins, Leukotrienes and Essential Fatty Acids
Volume65
Issue number2
DOIs
Publication statusPublished - Aug 2001

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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

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