Investigations on the role of arachidonic acid metabolism pathways in the antithrombotic activity of nafazatrom and molsidomine.
The activity of nafazatrom and molsidomine, two antithrombotic drugs claimed to increase prostacycline level, was investigated in an electrically-induced carotid thrombosis model in the conscious rat. Both nafazatrom (5 mg/kg, i.v.) and molsidomine significantly delayed thrombus formation, an activity that was shared by prostacyclin (100 ng/kg/min, i.v.). Acetylsalicylic acid, at a dosage devoided of antithrombotic activity (100 mg/kg, i.v.) abolished the effect of nafazatrom but not of molsidomine. These results indicate that a cyclooxygenase-dependent compound (prostacyclin ?) play a major role in the antithrombotic effect of nafazatrom but not of molsidomine. Moreover, since compounds inhibiting the lipoxygenase pathway, i.e., BW755c (10 and 25 mg/kg, i.v.) and nordihydroguaiaretic acid (10 and 25 mg/kg, i.v.) were unable to show any antithrombotic effect, the activity of molsidomine can unlikely be due to its lipoxygenase inhibitory property.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000188:drug therapy
D001095:Arachidonic Acids; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D047069:Pyrazolones; D016718:Arachidonic Acid; D008981:Molsidomine; D011464:Epoprostenol; C018845:nafazatrom