BUFFALO, N.Y. -- 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, via a novel pathway unrelated to its COX-2 inhibition.
University at Buffalo researchers discovered this unexpected finding while conducting basic research on potassium channels.
They found that low concentrations of the drug, corresponding to a standard prescription, reduced the heart rate and induced pronounced arrhythmia in fruit flies and the heart cells of rats.
The drug inhibited 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 study showed.
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, Ph.D., associate professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences and senior author on the study. Vioxx was withdrawn from the market in September 2004.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 drugs effect as a pain reducer, 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 research was supported by grants from the National Science Foundation to Singh and Randall D. Shortridge, Ph.D., UB assistant professor of biological sciences, to analyze the basic properties of potassium channels.
Aware that COX-2 inhibitors had been shown to produce cardiovascular side effects, the researchers first tested whether Celebrex would affect the heart in fruit flies, a goo
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