Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties.
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.
Kis
Bela
B
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. bkis@wfubmc.edu
Snipes
James A
JA
Busija
David W
DW
D000082:Acetaminophen / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D000082:Acetaminophen; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3