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Review
. 2005 Feb;72(2):85-7.
doi: 10.1016/j.plefa.2004.10.005.

COX-3 and the mechanism of action of paracetamol/acetaminophen

Regina Botting  1 , Samir S Ayoub
Affiliations
Review

COX-3 and the mechanism of action of paracetamol/acetaminophen

Regina Botting et al. Prostaglandins Leukot Essent Fatty Acids. 2005 Feb.

Abstract

Paracetamol produces analgesia in the mouse writhing test through a central action which is paralleled by a reduction in brain PGE(2) concentrations. In contrast, diclofenac has a peripheral analgesic action in this test. Paracetamol-induced hypothermia is also accompanied by a reduction in brain PGE(2) concentrations in C57/Bl6 mice. This hypothermic effect of paracetamol was reduced in COX-1 but not in COX-2 gene-deleted mice. These results support the view that analgesia and hypothermia due to paracetamol are mediated by inhibition of a third COX isoenzyme (designated COX-3). In cultured mouse macrophages, COX-2 is induced by treatment with LPS or with high concentrations of diclofenac. Diclofenac-induced COX-2 is inhibited with low concentrations of paracetamol, whereas LPS-induced COX-2 is insensitive to paracetamol inhibition. The mechanisms of induction and possibly the functions of these two COX-2 enzymes are also different.

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