An older nonsteroidal anti-inflammatory drug (NSAID) called dipyrone may offer a new approach to reducing injury to brain tissue after a stroke, according to a study in the October issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
Dipyrone reduces brain cell death in experimental models of stroke, suggesting that it "may be developed for use as a neuroprotective agent," concludes the report by Dr. Robert M. Friedlander and colleagues of University of Pittsburgh School of Medicine and Harvard Medical School.
Dipyrone Protects Against Programmed Cell Death
Dipyrone—also called metamizole—is an older NSAID, related to aspirin and ibuprofen. However, dipyrone is less frequently used since it was linked to a small risk of a serious complication called agranulocytosis, which causes severe loss of immune function. (Dipyrone is banned from clinical use in many countries including the United States, but is still used in other countries.)
The researchers screened more than 1,000 drugs to identify compounds with the ability to block the release of cytochrome c from cell mitochondria. This is a critical starting point in the process of brain cell death—called apoptosis—in response to lack of blood flow and oxygen supply to the brain in patients with stroke. Of all the drugs tested, dipyrone was extremely potent at very low concentrations.
Dr. Friedlander and colleagues performed a series of experiments to more fully evaluate dipyrone's possible neuroprotective properties. Studies on the cellular level confirmed that dipyrone blocked release of cytochrome c from mitochondria, thus disrupting the cascade of events leading to brain cell apoptosis. This effect was separate from the better-understood process by which dipyrone and other NSAIDs reduce pain and inflammation (namely, by blocking the enzyme cyclooxygenase).
After induced stroke in mice, dipyrone reduced the area of brain cell death by more than 40 percent, compared to an inactive treatment. The reduction in brain injury was accompanied by reductions in neurological and behavioral abnormalities typical of stroke. Dipyrone also reduced brain cell (neuron) abnormalities seen under the microscope.
Taken together, the results suggest that dipyrone might be developed into a new treatment to reduce brain damage after a stroke. The risk of agranulocytosis is still a concern; however, this complication is likely to be rare at the relatively low dipyrone doses used in the study.
While it has yet to be tried in human stroke patients, "Dipyrone is remarkably neuroprotective in cerebral ischemia," the researchers conclude. By interrupting a key step in the process of brain cell apoptosis, dipyrone may provide a new approach to limiting brain injury caused by stroke. More research will be needed to better understand how dipyrone exerts its neuroprotective effect.