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In a study to screen potential therapies for Parkinson’s disease, researchers at Duke University Medical Center have produced the first strong evidence that amphetamine derivatives such as 3,4-methylenedioxymethamphetamine (MDMA, also known as the street drug Ecstasy) play a direct role in signaling muscles to move (PloS Biol., published online Aug. 1, dx.doi.org/10.1371/journal.pbio.0030271).
Parkinson’s disease is marked by the progressive loss of dopamine neurons and corresponding deterioration of muscle control. The team, led by Tatyana D. Sotnikova, modified mice to stop recycling dopamine and to lower dopamine production to undetectable levels. The absence of dopamine caused the mice to exhibit extreme muscle rigidity and other symptoms of Parkinson’s disease.
The researchers used the dopamine-free mice to screen more than 70 compounds. They found that high concentrations of amphetamines, MDMA in particular, reversed some of the Parkinson’s-like symptoms via an unknown mechanism that appears to be unrelated to dopamine, serotonin, or norepinephrine neurotransmission. They believe the motion-inducing effect may be mediated by receptors for endogenous amphetamine-like amines, such as phenylethylamine.
The researchers also report a synergistic effect with MDMA and l-DOPA, the dopamine precursor commonly used in Parkinson’s therapy. They caution that further research is necessary before medical applications of these findings are considered.
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