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The thromboxane A2/prostaglandin endoperoxide receptor antagonist activity of CV-4151, a thromboxane A2 synthetase inhibitor

1988; Elsevier BV; Volume: 147; Issue: 3 Linguagem: Inglês

10.1016/0014-2999(88)90169-0

1879-0712

Yoshimi Imura, Zen-ichi Tereshita, Yumiko Shibouta, Kohei Nishikawa,

Receptor Mechanisms and Signaling

The thromboxane A2/prostaglandin endoperoxide (TXA2/PGH2) receptor antagonist activity of CV-4151, a potent TXA2 synthetase inhibitor, was examined. CV-4151 inhibited guinea pig and human platelet aggregation induced by U-44069 with IC50 values of 1.2 ± 0.3 × 10−5 and 1.9 ± 0.4 × 10−5 M, respectively, and inhibited the specific binding of [3H]U-46619 to washed guinea pig and human platelets with IC50 values of 1.2 ± 0.3 × 10−6 and 5.1 ± 1.0 × 10−6 M, respectively. CV-4151 competitively inhibited the contraction of rabbit aortic strips induced by U-44069 with a pA2 value of 5.90. In experiments in mice in vivo, CV-4151 (1 and 10 mg/kg i.v.) significantly inhibited the thrombocytopenia induced by U-44069 in a dose-dependent manner. These results show that CV-4151 has a distinct TXA2/PGH2 receptor antagonist effect, and that this effect together with its inhibition of TXA2 synthetase could be important for the pharmacological action of this compound.