title: Investigations on the role of arachidonic acid metabolism pathways in the antithrombotic activity of nafazatrom and molsidomine.
abstract: 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.
mesh_terms: 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
chemical_list: D001095:Arachidonic Acids; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D047069:Pyrazolones; D016718:Arachidonic Acid; D008981:Molsidomine; D011464:Epoprostenol; C018845:nafazatrom