Comparison of the inhibitory effects of acetylsalicylic acid and trifusal on enzymes related to thrombosis.
Triflusal is a new antithrombotic agent, structurally similar to acetylsalicylic acid (ASA), which has been shown to possess a different pharmacological profile, suggesting a different mechanism of action for both compounds. To confirm this hypothesis we have studied, comparatively, the inhibition by  triflusal and ASA of the activity of several enzymes involved in the equilibrium of platelet haemostasis, namely, prostaglandin-synthetase system (PG-synthetase), cyclo-oxygenase, thromboxane-synthetase and cAMP-phosphodiesterase. Results indicate that trilfusal is 60% less potent as inhibitor of cyclooxygenase (biological method) and of prostaglandin biosynthesis (spectrophotometric method ) than ASA. On the contrary, triflusal is five times more potent than ASA as inhibitor of cAMP phosphodoesterase. Inhibition of thromboxane-synthetase by both compounds is negligible and without physiological significance. These results suggest a mechanism of action of trifusal that might explain the different pharmacological profile between triflusal and ASA as antithrombotic agents.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002417:Cattle; D016861:Cyclooxygenase Inhibitors; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006736:Horses; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D012459:Salicylates / Q000494:pharmacology*; D012756:Sheep; D013927:Thrombosis / Q000201:enzymology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D005343:Fibrinolytic Agents; D012459:Salicylates; C016167:triflusal; D010088:Oxidoreductases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D013930:Thromboxane-A Synthase; D001241:Aspirin