Amphetamines Improve Parkinson's Symptoms in Mice

Finding could lead to new ways to treat neurodegenerative disease

THURSDAY, Aug. 4, 2005 (HealthDay News) -- Experiments in mice reveal that amphetamines, including the drug known as Ecstasy, can reverse some of the symptoms of Parkinson's disease.

However, the researchers caution that their findings do not mean that Parkinson's disease patients should try to treat themselves with amphetamines. The findings do suggest that similar drugs might be useful when given with current therapies, such as L-DOPA.

The report appears in the August issue of PLoS Biology.

"We have a new and exciting hypothesis that involves a new system that controls movement in the absence of dopamine," said lead researcher Marc G. Caron, a professor of cell biology at Duke University Medical Center.

Dopamine is a chemical that sends messages from the brain to other cells to help control movement, and is partially lacking in people with Parkinson's. The use of the dopamine replacement L-DOPA is the hallmark of Parkinson's treatment. While L-DOPA is effective, it is associated with sometimes severe side effects and diminishing effectiveness over time.

Caron's team used mice that couldn't recycle or manufacture dopamine. Since these mice lacked dopamine, they showed the symptoms of Parkinson's disease. The symptoms lasted for up to 16 hours. Symptoms included impaired movement, rigidity and tremor. However, when the mice were given L-DOPA, the Parkinson's symptoms disappeared.

When Caron's group gave these mice high doses of amphetamine derivatives such as methamphetamine and MDMA, known as Ecstasy, the Parkinson's symptoms were partially reversed. "The mice recovered a lot of their normal movement," Caron said.

In addition, the researchers found that low doses of amphetamines, when combined with low doses of L-DOPA, also reversed Parkinson's symptoms. "The drugs are synergistic," Caron said. "When given together, the mice recovered their normal movements."

Despite these findings, Caron doesn't recommend amphetamines as a treatment for Parkinson's. "We are cautious, because amphetamines are controversial," Caron said. "You don't want to suggest that Parkinson's patients should stand on the street corner and deal amphetamines."

Caron's team is looking for other compounds that affect movement without the psychoactive effects of amphetamines, but that can be used in combination with L-DOPA to treat Parkinson's disease. "It's a new idea," Caron said. "But who knows? Time will tell."

One Parkinson's expert doesn't think that using these mice is a way to find new ways of treating the disease. "In this case, the very fact that their model is acute makes it different from Parkinson's disease, which is chronic," said Michael J. Zigmond, co-director of the Center for Neuroscience at the University of Pittsburgh School of Medicine.

"Indeed, what the field needs is not so much new drugs to reverse the symptoms of dopamine loss, but drugs that either do not cause the dyskinesia associated with chronic treatment or are neuroprotective rather than only offering symptomatic treatment. The authors' model will not be useful to assess either type of drug," Zigmond said.

Zigmond believes that the future direction of Parkinson's treatments will be in developing drugs that inhibit the ability of defective proteins to develop in cells. "A lot of degenerative diseases are caused by an accumulation of misfolded proteins, which chokes the cell to death," he said. This is also true in Alzheimer's disease, Huntington's disease and ALS, Zigmond noted.

Parkinson's is much more complicated than just the movement disorders, which are its obvious symptoms, Zigmond added. "We now realize that we have more to know than we thought we needed to know five years ago," he said. "Understanding Parkinson's disease is getting more complicated."

Almost 500,000 Americans suffer from Parkinson's disease, according to the National Institute of Neurological Disorders and Stroke, and 50,000 are diagnosed annually. In addition to tremors, slow movement or rigidity, progression of the disease also leads to severe impairment in cognitive function.

More information

The National Institute of Neurological Disorders and Stroke can tell you more about Parkinson's disease.

SOURCES: Marc G. Caron, Ph.D., professor, cell biology, Duke University Medical Center, Durham, N.C.; Michael J. Zigmond, Ph.D., co-director, Center for Neuroscience, University of Pittsburgh School of Medicine, Pa.; August 2005 PLoS Biology
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