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Received for publication February 28, 2005.
Revised April 12, 2005.
Accepted for publication May 5, 2005.
Cyclooxygenase-3 (COX-3), a novel COX splice variant, was suggested as the key to unlocking the mystery of the mechanism of action of acetaminophen. While COX-3 might have COX activity in canine, and this activity might be inhibited by acetaminophen, its low expression level and the kinetics indicate unlikely clinical relevance. In rodents and humans COX-3 encodes proteins with completely different amino acid sequences than COX-1 or COX-2 and without COX activity, therefore it is improbable that COX-3 in these species plays a role in prostaglandin-mediated fever and pain. The aim of this review is an evaluation of the literature which seeks to point out critical theoretical and methodological limitations of the COX-3 studies which led several investigators to scientifically questionable conclusions.
Key words:
COX-3, acetaminophen, cyclooxygenase, fever, pain, prostaglandin
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