Enzyme Inhibited by Acetaminophen Identified

Researchers have found a novel cyclo-oxygenase enzyme (COX-3) that is inhibited by acetaminophen and may explain the mode of action of this drug. The finding was published in the September 23, 2002, issue of the Proceedings of the National Academy of Sciences.

Acetaminophen relieves pain and fever, but not inflammation, and is a very poor inhibitor of the other two known cyclo-oxygenases, COX-1 and COX-2.

COX-3 was initially isolated from canine brains. Then, working with insect cells grown in tissue culture, investigators from Brigham Young University (Salt Lake City, UT, USA; www.byu.edu) tested the new enzyme against pain-relieving drugs and found that it was sensitive to acetaminophen and other similar drugs. COX-3 was also identified in human tissue and found to be expressed at the highest levels in the heart and brain.

"Since the discovery of COX-2, we have learned an enormous amount about how aspirin drugs work,” explained senior author Dr. Dan Simmons, professor of biochemistry at Brigham Young. "However, a number of questions, such as the mechanism of acetaminophen, have remained elusive. We have found a previously unidentified enzyme that is inhibited by acetaminophen. Hopefully, this enzyme, COX-3, is the target of this drug that inhibits pain and fever.




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