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Mechanism of acetaminophen inhibition of cyclooxygenase isoforms.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2001 Mar 15; Vol. 387 (2), pp. 273-80. - Publication Year :
- 2001
-
Abstract
- Acetaminophen has similar analgesic and antipyretic properties to nonsteroidal antiinflammatory drugs (NSAIDs), which act via inhibition of cyclooxygenase enzymes. However, unlike NSAIDs, acetaminophen is at best weakly antiinflammatory. The mechanism by which acetaminophen exerts its therapeutic action has yet to be fully determined, as under most circumstances, acetaminophen is a very weak cyclooxygenase inhibitor. The potency of acetaminophen against both purified ovine cyclooxygenase-1 (oCOX-1) and human cyclooxygenase-2 (hCOX-2) was increased approximately 30-fold by the presence of glutathione peroxidase and glutathione to give IC50 values of 33 microM and 980 microM, respectively. Acetaminophen was found to be a good reducing agent of both oCOX-1 and hCOX-2. The results are consistent with a mechanism of inhibition of acetaminophen in which it acts to reduce the active oxidized form of COX to the resting form. Inhibition would therefore be more effective under conditions of low peroxide concentration, consistent with the known tissue selectivity of acetaminophen.
- Subjects :
- Acetaminophen chemistry
Animals
Binding, Competitive drug effects
Cyclooxygenase 1
Cyclooxygenase 2
Enzyme Activation drug effects
Glutathione chemistry
Glutathione Peroxidase chemistry
Humans
Hydrogen Peroxide chemistry
Hydrogen Peroxide pharmacology
Ibuprofen pharmacology
Indomethacin pharmacology
Isoenzymes chemistry
Linoleic Acids chemistry
Lipid Peroxides chemistry
Membrane Proteins
Oxidation-Reduction drug effects
Prostaglandin-Endoperoxide Synthases chemistry
Reducing Agents chemistry
Reducing Agents pharmacology
Sheep
Acetaminophen pharmacology
Isoenzymes antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9861
- Volume :
- 387
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 11370851
- Full Text :
- https://doi.org/10.1006/abbi.2000.2232