Paracetamol (which is a recommended international nonproprietary name of acetaminophen (acetyl-p-aminophenol, APAP)), was synthesized in 1878 by Morse and first introduced into medicine as an antipyretic/analgesic by Von Mering in 1893. 1-3 Initially, it was rarely used in favor of phenacetin. However, after discovering that paracetamol is the main metabolite of phenacetin with better tolerance vs. phenacetin nephrotoxicity, in the 1950s paracetamol replaced phenacetin in use 4-6 and has become a widespread drug since then. Prostaglandins are mainly mediators of inflammatory pain. 7,8 The enzymes responsible for the synthesis of these mediators are called cyclooxygenases. 9 In 1971, John Vane identified the first cyclooxygenase (COX-1). 10 This discovery helped explain the mechanism of action of aspirin, which has been extensively used since 1899 as an analgesic and anti-inflammatory drug. 10 Afterwards, in 1991, Xie et al at Daniel Simmons's laboratory, Brigham Young University, discovered the second cyclooxygenase (COX-2). 11,12 Interestingly, the structure of the COX-2 enzyme did not differ substantially from the previously discovered COX-1. 13 However, they have different clinical significance. 14,15 Finally, in 2002, Chandrasekharan et al discovered

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