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Old Drug May Have New Use in Protecting Brain

Dipyrone Could Help to Limit Brain Injury after Stroke

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  Neurosurgeryofficial 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.

About  Neurosurgery
Neurosurgerythe Official Journal of the  Congress of Neurological Surgeons, is your most complete window to the contemporary field of neurosurgery. Members of the Congress and non-member subscribers receive 3,000 pages per year packed with the very latest science, technology, and medicine, not to mention full-text online access to the world's most complete, up-to-the-minute neurosurgery resource. For professionals aware of the rapid pace of developments in the field,  Neurosurgery is nothing short of indispensable.

About Lippincott Williams & Wilkins

Lippincott Williams & Wilkins (LWW) is a leading international publisher for healthcare professionals and students with nearly 300 periodicals and 1,500 books in more than 100 disciplines publishing under the  LWW brand, as well as content-based sites and online corporate and customer services.

LWW is part of  Wolters Kluwer Health, a leading global provider of information, business intelligence and point-of-care solutions for the healthcare industry. Wolters Kluwer Health is part of  Wolters Kluwer, a market-leading global information services company with 2010 annual revenues of €3.6 billion ($4.7 billion).