Salicylamide reverses the aspirin-antagonistic effect of salicylic acid on rat platelet cyclooxygenase.
The antagonistic effect of salicylic acid (SA), the major metabolite of aspirin, on aspirin (ASA)-induced inhibition of cyclooxygenase has been recognized in vivo and in vitro. Salicylamide is available with aspirin in some analgesic preparations. Salicylamide shares important characteristics with salicylic acid including the lack of effect on cyclooxygenase and platelet aggregation as well as a close structural resemblance. This prompted us to study the interaction of salicylamide with aspirin and/or SA on rat platelet and cyclooxygenase. Our results showed that salicylamide has, unlike SA, no blocking effect on the anticyclooxygenase effect of aspirin in vitro. Moreover, salicylamide could dose-dependently prevent the aspirin-blocking effect of SA on platelet cyclooxygenase. These results suggest that salicylamide and SA compete for a receptor on cyclooxygenase different to that of aspirin. A functional model of cyclooxygenase enzyme is proposed.
Department of Pharmacology and Toxicology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
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D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D013929:Thromboxane B2 / Q000096:biosynthesis
D016861:Cyclooxygenase Inhibitors; D012457:Salicylamides; D012459:Salicylates; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; C031060:salicylamide; D020156:Salicylic Acid; D001241:Aspirin