COX-1 and COX-2 enzymes may be blocked by pain medications

May 30, 2006

COX-1 and COX-2 enzymes may be blocked by pain medications such as

Advil and Vioxx in a more complex manner than was previously

understood, a Queen's University study has found.

" The results of the study have potential implications for how we

classify the commonly used anti-inflammatory and pain drugs for

aches, pains, and fever, " says Colin Funk, a professor of

Biochemistry and Physiology at Queen's and Canada Research Chair in

Molecular, Cellular and Physiologiocal Medicine.

Published on-line in Nature Medicine, the study was conducted in

collaboration with University of Pennsylvania researchers.

The study was initiated to explore the biochemistry associated with

COX-2 inhibitors such as Vioxx, Bextra and Celebrex, which are now

associated with an increased incidence of heart attack and stroke.

Researchers looked at mice that were genetically modified so that

their COX-2 was inhibited - to create a physiology in mice that

roughly mimics that of users of COX-2 inhibitors. They found that the

COX-1 enzymes in the mice " hooked up " in an unanticipated way with

their remaining COX-2 enzymes creating what is called a new

heterodimer.

Dr. Funk's co-researcher, Queen's biochemist , has

developed a computer model to show how the COX-1/COX-2 molecules can

associate.

" It's possible the COX-2 inhibitor medications may affect the

resulting new enzyme which is a mix of COX-1 and COX-2, " says Dr.

Funk.

This effect is being further explored by scientists and may lead to a

broadened understanding of the biochemistry of common pain

medications. It is now pointing toward possible alternatives to drugs

like Vioxx and Celebrex, says Dr. Funk.

A study published April 13 by The Journal of Clinical Investigation

(JCI) by the same research team found that new types of anti-

inflammatory drugs may reduce COX-2 cardiovascular problems. That

study was conducted after this one and incorporated the genetically

modified mice created in this study.

The JCI study found a drug target that might substitute for COX-2: an

enzyme called microsomal prostaglandin E synthase (mPGES)-1. The

researchers showed that this drug did not predispose the animals to

thrombosis or elevate blood pressure.

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