Symptoms in mice that mimic Parkinson鈥檚 disease are reversed by treatment with amphetamines, including Ecstasy, according to a new study.
The drugs seem to work through a pathway not involving the chemical dopamine, which surprised the researchers since dopamine deficiency is the cause of Parkinson鈥檚.
These results may lead to the discovery of 鈥渙ther systems that can replace or substitute for the very important action of dopamine鈥�, says study author Marc Caron of Duke University, US.
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Dopamine transmission in a region of the brain called the striatum is essential for normal movement. Parkinson鈥檚 results when dopamine-producing neurons in this region die.
The best current treatment for the condition is a chemical called L-Dopa 鈥� a natural precursor to dopamine. L-Dopa works well for patients in the early stages of the disease, but its effectiveness diminishes with time, and it can actually cause involuntary movements.
Unknown system
To screen for other types of drugs, Russian scientists Tatyana Sotnikova and Raul Gainetdinov, working with the team at Duke University, studied mice altered to possess no brain dopamine. They show classic symptoms of Parkinson鈥檚 disease including muscle rigidity, problems initiating movement, and resting body tremor.
When the researchers treated these mice with high doses of different types of amphetamines, their movement problems dramatically improved. The most effective compound was methylenedioxymethamphetamine (MDMA) 鈥� commonly known as Ecstasy.
This result was surprising, because amphetamines are thought to affect movement through the dopamine system. But since these mice have no functional dopamine system, an unknown mechanism must be at work.
The authors suggest proteins called trace amine receptors may be involved. Amphetamines interact with these receptors, but very little is known about their physiological role in the brain.
Ecstasy-Parkinson鈥檚 links
Some previous research has hinted that Ecstasy might actually cause symptoms of Parkinson鈥檚 disease, although the best-known study was retracted when the researchers discovered they had administered the wrong drug.
Prompted by British stuntman Tim Lawrence鈥檚 claim that his Parkinson鈥檚 symptoms were relieved by Ecstasy, a study in marmoset monkeys confirmed some anti-Parkinsonian effects the drug. And work by Werner Schmidt and colleagues at the University of T眉bingen, Germany, has shown similar results in rats.
The Duke University researchers used a very different approach and a very different method, Schmidt notes, but they 鈥渞eached the same conclusions as we did鈥�.
鈥淲e have to be cautious not to be too suggestive, so that every Parkinson鈥檚 patient doesn鈥檛 run to the street corner,鈥� Caron warns.
The researchers plan to base further work around the structure of amphetamines, Caron says, to find or create other compounds that might have similar anti-Parkinsonian effects.
Journal reference: Public Library of Science Biology (vol 3, p e271)
