RT Journal Article
SR Electronic
T1 Acetaminophen and the Cyclooxygenase-3 Puzzle: Sorting out Facts, Fictions, and Uncertainties
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 7
DO 10.1124/jpet.105.085431
VO 315
IS 1
A1 Bela Kis
A1 James A. Snipes
A1 David W. Busija
YR 2005
UL http://jpet.aspetjournals.org/content/315/1/1.abstract
AB Cyclooxygenase (COX)-3, a novel COX splice variant, was suggested as the key to unlocking the mystery of the mechanism of action of acetaminophen. Although COX-3 might have COX activity in canines, 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 to evaluate the literature that seeks to point out critical theoretical and methodological limitations of the COX-3 studies that led several investigators to scientifically questionable conclusions. The American Society for Pharmacology and Experimental Therapeutics