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Researchers Morph Morphine-Like Drugs

Develop painkiller minus the potentially deadly side effects

MONDAY, March 24, 2003 (HealthDayNews) -- As the war in Iraq rages on, more soldiers will inevitably be wounded. One of the first things medical personnel try to do for these soldiers is reduce the pain they're feeling, but powerful pain medications such as morphine can have lethal side effects for wounded servicemen.

That's why researchers from the University of Arizona and the University of New England have been working on creating a new type of pain-relieving medication, called glycosylated enkephalins, that works without causing those potentially deadly reactions.

In rodent studies they've had success, reports one of the researchers at a presentation March 24 at the American Chemical Society's annual meeting in New Orleans.

"What we've found in mice and rats is that these drugs are two to three times the potency of morphine and seem to be devoid of side effects," says one of the researchers, Robin Polt, a professor of chemistry at the University of Arizona in Tucson.

The problem with morphine and other narcotic pain relievers is that they can be habit-forming and they can cause nausea, vomiting, dizziness and fainting, according to the National Library of Medicine.

In battlefield situations, Polt says morphine can be deadly for wounded soldiers who have lost a lot of blood. He explains that because of the blood loss, morphine injected at the wound site tends to stay there. Because it doesn't circulate through the bloodstream, it doesn't give pain relief, and so more morphine is injected. Later, when a soldier receives a blood transfusion and normal blood circulation is restored, all of that morphine is finally released into the system and can cause a toxic reaction, Polt explains.

So Polt and his colleagues set out to make a painkiller that wouldn't create these problems.

Polt says that in the 1970s, scientists discovered natural painkilling peptides in the brain, known as enkephalins. Enkephalins work by binding to the same pain receptors in the brain that morphine does. Initial excitement over the discovery of enkephalins quickly died down, however, when researchers realized that synthetic enkephalins couldn't pass through the blood-brain barrier. The blood-brain barrier is a membrane that stops toxins from reaching the brain.

But Polt and his colleagues have discovered a way to trick the body to allow man-made enkephalins to enter the brain. By attaching a simple glucose molecule to enkephalins, the medication can pass through the blood-brain barrier and seek out the pain receptors in the brain.

Polt says they've tested the new compound on mice and rats and found it worked well without causing narcotic-like side effects.

"These drugs are more remarkable for what they don't do," he says, pointing out they didn't cause the euphoria that morphine does and seemed to be "devoid of side effects."

What's most exciting about this work, says Polt, is that it could pave the way for more effective drugs in the future.

"There are about 250 peptides that the brain produces. If this works for even a fraction of those, it could open up a way to make whole new classes of drugs," explains Polt. "It will lead to much better drugs than we have today with fewer side effects."

Dr. Michel Dubois, director of the pain management center at New York University Medical Center says this research is "exciting" and "worth pursuing." He cautions, however, that "this is still a very long way from even thinking about using it clinically."

He explains that while rodent studies are a good for initial assessments, they're no substitute for humans. Polt says the research will be continuing to the next step, which is larger animals such as pigs.

Dubois adds, "This is a very active field of medical research, but so far it's been a little like the search for the Holy Grail."

More information

To learn more about pain medications, visit the National Library of Medicine or the American Academy of Family Physicians.

SOURCES: Robin Polt, Ph.D., professor, chemistry, University of Arizona, Tucson; Michel Dubois, M.D., director, pain management center, New York University Medical Center, and anesthesiologist, New York University School of Medicine, New York City; March 24, 2003, presentation, American Chemical Society annual meeting, New Orleans
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