Inhibition of arterial thrombosis and platelet function by nafazatrom.
Nafazatrom (1-[2-(naphthyloxy) ethyl]3-methyl-2-pyrayolin-5-one) has been shown to be a potent antithrombotic agent in experimental animals, but its mode of action is unknown. In this study, we examined its antithrombotic effect on arterial and venous thrombosis, vessel wall prostacyclin synthesis, and platelet aggregation in vivo and ex vivo in the rabbit. We found that arterial but not venous thrombus formation was significantly inhibited with low doses of nafazatrom. This antithrombotic effect was associated with a normalization of reduced platelet survival. Nafazatrom had no effect on basal or stimulated prostacyclin production but inhibited ADP- and collagen-induced platelet aggregation in vivo and ex vivo. This platelet effect was associated with a reduction in platelet thromboxane B2 release and an inhibition of irreversible ADP-induced platelet aggregation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D011464:Epoprostenol / Q000096:biosynthesis; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D011460:Prostaglandins F / Q000097:blood; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D011817:Rabbits; D013927:Thrombosis / Q000517:prevention & control*
D005343:Fibrinolytic Agents; D011460:Prostaglandins F; D011720:Pyrazoles; D047069:Pyrazolones; D000244:Adenosine Diphosphate; D011464:Epoprostenol; C018845:nafazatrom; C100006:prostaglandin F1