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Popular arthritis drug can disrupt heart rhythm

Celebrex, a popular arthritis drug that blocks pain by inhibiting an enzyme known as COX-2, has been shown in laboratory studies to induce arrhythmia, or irregular beating of the heart.

 

Researchers at the University at Buffalo in the USA, conducting basic research on potassium channels, found that low concentrations of the drug, equivalent to a standard prescription, reduced the heart rate and induced pronounced arrhythmia in fruit flies and the heart cells of rats.

 

Celebrex was found to inhibit the normal passage of potassium ions into and out of heart cells through pores in the cell membrane known as delayed rectifier potassium channels.

 

“The adverse effects of drugs like Celebrex and Vioxx based on their selective inhibition of COX-2 currently are a topic of intense discussion in the medical community,” said Satpal Singh, PhD, associate professor of pharmacology and toxicology in the UB School of Medicine and senior author on the study, which appears in the Journal of Biological Chemistry. Vioxx was withdrawn from the market in September 2004.

 

“We now have shown an important new effect of Celebrex through a totally different pathway, one that is unrelated to the drug’s effect as a pain reducer,” associate professor Singh said. “The adverse effect arising from this unexpected mechanism definitely needs to be studied more closely, because the potassium channels inhibited by the drug are present in heart, brain and many other tissues in the human body.”

 

The researchers now are examining the underlying molecular mechanisms responsible for the drug’s action and its effect on other ion channels that play a prominent role in setting the rhythm of the heart.

 

“We are trying to determine whether the drug binds directly to the channels or to some other molecule, and if it acts by blocking the pore of the channel through which potassium ions travel or by some other mechanism,” ass prof Singh said.

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