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Compound May Ease Side Effects of Parkinson's Drug Tue May 13, 2003 01:37 PM ET By Keith Mulvihill NEW YORK (Reuters Health) - Animal research suggests an experimental drug may counteract a common and debilitating side effect of levodopa, the most widely used drug for Parkinson's disease, French scientists report. They found that in monkeys with Parkinson-like symptoms, the compound eased levodopa-associated dyskinesia -- involuntary movements of mouth, face and limbs that are a frequent side effect of the drug in people with Parkinson's. The encouraging results, published this week in the advance online edition of the journal Nature Medicine, should give the green light for clinical trials of the drug in patients with Parkinson's, according to the study's authors. Parkinson's disease is a progressive, neurological disorder that causes tremor, muscle rigidity and movement problems. The disease involves a loss of cells in the brain that produce the chemical dopamine, which plays a key role in regulating movement. The main treatment is the drug levodopa, or L-dopa, which helps restore diminishing levels of dopamine in Parkinson's patients. But long-term use of the drug often leads to potentially disabling side effects. Roughly 40 percent of Parkinson's patients taking L-dopa will develop dyskinesia after four to five years of treatment, explained lead investigator Dr. Pierre Sokoloff of INSERM in Paris, in an email interview. "There is no current safe therapeutic cure of dyskinesia," said Sokoloff, noting that "the only one that has been introduced into the clinics, amantadine, is partly efficacious and can induce psychiatric troubles." "Thus, minimizing dyskinesia is a major concern in the management of Parkinson's disease," he added. Previously, it was discovered that L-dopa works by attaching to a receptor on cells called D3. In the current study, the researchers studied the effects of L-dopa when it is combined with another compound called BP 897 that mimics dopamine and also binds to the D3 receptor. "The study shows that the D3 receptor is specifically involved in both the therapeutic effect and dyskinesia produced by L-dopa," said Sokoloff. "The novel finding in the study is that it points to a major role of a particular receptor for dopamine, the D3 receptor, which (was) discovered in 1990, and whose role in Parkinson's disease has not been previously demonstrated," he added. Given the dual role of the D3 receptor, Sokoloff's team hoped to fine- tune its function, he explained. This was achieved by administering BP 897, a mimetic of dopamine, acting selectively at the D3 receptor. However, BP 897 only partially mimics dopamine, so that it preserves the therapeutic response of L- dopa and avoids excessive receptor stimulation that leads to dyskinesia, according to Sokoloff. "The next step is clinical trials with Parkinson's disease patients," the researcher said. "Although the animal model we have used produces symptoms remarkably similar to Parkinson's disease, there is always a piece of uncertainty when going from animals to humans." SOURCE: Nature Medicine 2003;10.1038/nm875. SOURCE: Reuters Health http://reuters.com/newsArticle.jhtml?type=healthNews&storyID=2733825 * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn