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Morphine-like Painkiller Appears to be Less Addictive

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www.ProHealth.com • April 4, 2003


Move over morphine, researchers at the University of Arizona and the University of New England have developed a new narcotic based on a natural painkiller found in the body that appears to be more potent but less addictive.

Although researchers have developed many narcotic-type painkillers that rival morphine in strength, few have had the ability to avoid its potential side effects, until now. These side effects include severe constipation, reduced blood pressure and breathing, and addiction.

"This represents one of the most promising morphine-like painkillers to date in terms of avoiding its side effects, particularly addiction," says Robin Polt, Ph.D., a professor of chemistry at the University of Arizona in Tucson and a chief researcher on the project. He presented details of the research today at the 225th national meeting of the American Chemical Society.

Called a glycosylated enkephalin, the compound appears promising in studies using mice. If it works in humans, it could be a safer alternative for people who are allergic to morphine or cannot take the drug because of concern for its side effects, the researchers say.

"Our hope is that glycosylated enkephalins can be used to block pain in severe trauma injuries, in victims who could not normally receive narcotics," says Polt, who is currently serving as a visiting scientist at the National Science Foundation in Arlington, Va.

Morphine, one of the most potent pain relievers available, is beneficial to both cancer and trauma patients. However, its potential side effects have limited its use.

For years, researchers have sought to find a drug that could block pain the same way that morphine does without its negative side effects. In the 1970s, scientists discovered enkephalins, small proteins that are naturally produced by the body to reduce pain.

Synthetic analogs of enkephalins seemed to fit the bill, but they soon ran into a major problem that rendered them ineffective: the blood-brain barrier, a biological membrane that blocks toxins from entering the brain.

"Unfortunately, the blood-brain barrier stops most small peptides, including the enkephalins, from entering the brain," Polt says.

After years of experimentation, Polt and his associates recently discovered that attaching a glucose molecule to the enkephalins permits them to penetrate the blood-brain barrier, allowing them to attach to pain receptors in the brain and reduce pain in a manner similar to morphine.

Although other peptides have been developed that can cross the blood brain barrier, few have done so with the ease of the new drug, Polt says.

One of Polt's associates, Edward J. Bilsky, Ph.D., of the University of New England, recently conducted tests in which mice were injected with the experimental compound that had two to three times the potency of morphine. Further studies in mice indicate that the drug had significantly fewer side effects and was less toxic than morphine and related narcotics. The drug triggered behavior that was consistent with less addiction.

Polt believes that this research opens up the door to a whole new class of compounds based on brain peptides. Newer synthetic analogues of the naturally occurring peptides can be created that can similarly be linked to carbohydrate molecules in order to pass through the blood- brain barrier and reach their specific targets in the brain. These drugs may hold promise for problems related to memory, attention and even depression, he says.

These glycosylated neuropeptides, as they are called, have two main advantages. First, they are easily degraded into amino acids and sugars in the body, which reduces their risk of toxicity. In addition, they are more specific in their action with the brain's receptors, which means fewer side effects.

For now, researchers continue to work on reducing any possible side effects associated with this new class of drugs. More work is needed before the drugs can be used in humans; additional animal studies are now planned. If all goes well, an actual drug could be available in five to 10 years, says Polt.

Although it will likely be initially administered by injection, developing the drug as an oral pill is now under consideration, he says.



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