Targeted Therapy Has New Target - Pain

Gleevec reformulated eliminates morphine tolerance in animal study

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(RxWiki News) As one of the first targeted therapies, Gleevec (imatinib) totally changed the care and outlook for people diagnosed with chronic myeloid leukemia (CML). With a bit of tweaking, this drug may be used to treat another chronic condition - pain.

Narcotics, including morphine, are the only real tool in the pharmaceutical arsenal to treat chronic pain. However, over time, individuals need more and more of a drug to find relief, eventually developing tolerance, at which point the medicine no longer works.

Researchers at The University of Texas MD Anderson Cancer Center have found that a reformulated version of Gleevec helped to eliminate morphine tolerance in mice.

"Ask your doctor what other drugs are available to treat your condition."

“By suggesting a way to prevent or reverse tolerance in patients, this study could have far-reaching implications for many people suffering with chronic intractable pain,” said senior author Howard B. Gutstein, M.D., professor in the Departments of Anesthesiology/Perioperative Medicine and Biochemistry at MD Anderson.

For this research, scientists discovered that activating the protein called platelet-derived growth factor receptor (PDGFR) made morphine no longer work in animals that had not ever been exposed to the narcotic.

Gleevec, which is approved to treat various kinds of leukemia and gastrointestinal cancers, targets and attacks a number of cell receptors including PDGFR, which is seen in high levels in cancer cells.

The drug has not been seen to affect morphine tolerance because it doesn't enter the nervous system. So Gutstein's team reformulated Gleevec with one molecule, which increased the drug's penetration into the brain.

This reformulated version not only prevented morphine tolerance, but totally reversed tolerance in rats that had been exposed to high doses of morphine continuously for several days.

Dr. Gustein says this is an exciting finding because Gleevec has already been approved in human. He adds that of course more animal studies and clinical trials will have to be conducted to test safety and effectiveness of the new formula.

“Many patients in severe pain often refuse high doses of opioids because of the side effects, and they desperately need relief,” Dr. Gutstein said. “We may be able to quickly translate this discovery and dramatically reduce the suffering endured by the sickest patients, and not just those with cancer.”

This study was funded by research grants from the U.S. National Institute on Drug Abuse and the U.S. National Institute on Alcohol Abuse and Alcoholism.

The authors have no competing financial interests.

Last Updated:
February 21, 2012