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Celebrex, a popular arthritis medication that obstructs 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 primary research on potassium channels.
They found that minimal concentrations of the medication, corresponding to a standard prescription, reduced the heart rate and induced pronounced arrhythmia in fruit flies and the heart cells of rats.
The drug inhibits 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 side 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, according to Satpal Singh, Ph.D., associate professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences and senior author of the current study. Vioxx was withdrawn from the market last September 2004.
We now have shown a necessary new effect of Celebrex through a totally different pathway, one that is unrelated to the medication effect as a pain reducer, Singh said. The side effect arising from this unexpected mechanism definitely needs to be studied more closely, because the potassium channels inhibits by the medication 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, assistant professor of biological sciences, to analyze the primary properties of potassium channels.
Aware that COX-2 inhibitors had been shown to produce cardiovascular adverse effects, the researchers first tested whether Celebrex would affect the heart in fruit flies, a good animal system for studies on heart in other species, including humans.