The Inhibitory Effect of GR32191, a Thromboxane Receptor Blocking Drug, on Human Platelet Aggregation, Adhesion and Secretion

Summary

GR32191, a potent selective thromboxane receptor antagonist, has been shown to inhibit completely prostaglandin endoperoxide and thromboxane A₂ (TxA₂)-induced platelet aggregation, [¹⁴C]-serotonin secretion and β-thromboglobulin secretion. Deposition of human platelets onto damaged rabbit aorta in vitro is reduced in the presence of GR32191 which appears to inhibit aggregation of platelets but not direct adhesion of platelets to subendothelium. The effects of non-prostanoid platelet activating agents whose mode of action requires the biosynthesis of TxA₂ are also inhibited by GR32191. Prostanoids which inhibit platelet function, such as prostacyclin or PGD₂, retain their inhibitory properties in the presence of GR32191 which does not inhibit phospholipase A₂, prostaglandin cyclooxygenase, thromboxane synthase, 12-lipoxygenase or cAMP phosphodiesterase activity. The inhibitory action of GR32191 on platelet aggregation, mural thrombus formation and platelet protein storage granule secretion suggests that it has potential in treatingthrombotic disease in man.

Keywords

GR32191 - Thromboxane receptor antagonist - Adhesion - Secretion - Platelet aggregation

• References

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