01 Sep 2005(Medical News Today) - The debilitating effects of
Parkinson's disease are well known: muscle rigidity, impaired
movement, and the uncontrollable shaking that makes even the most
mundane activity a challenge. The symptoms result from a progressive
deterioration of neurons, found in the midbrain, that produce
dopamine. With no cure on the horizon, the most common treatment
involves administration of the dopamine precursor, L-DOPA, usually in
pill form. Though symptoms subside at first, this treatment is
rendered ineffective over time.
In a new study reported in the open-access journal PLoS Biology,
Tatyana Sotnikova and colleagues from Duke University create a mouse
model that recapitulates many of the symptoms of Parkinson's disease
and use it to screen potential therapeutic drugs. By eliminating the
dopamine transporter - the protein responsible for recycling the
chemical into neurons - in mice, the authors reduced dopamine levels
in the midbrain by 20-fold. In addition, chemically inhibiting
dopamine production in these mice resulted in essentially
unmeasurable levels of the neurotransmitter, since it could now
neither be produced at normal levels nor be recycled.

The authors tested a number of drugs at various doses and found that
in addition to L-DOPA-related treatments, drugs related to
amphetamine were effective in ameliorating muscle rigidity, tremor,
and impaired movement in these mice. Most effective was
methylenedioxymethamphetamine HCl (MDMA), commonly known as ecstasy.
It has been shown that amphetamines can trigger release of
neurotransmitters such as dopamine, serotonin, and norepinephrine and
cause sudden bursts in neurotransmission, leading to a feeling of
alertness, increased muscular activity, and reduced fatigue. This
study, however, shows that treating mice with MDMA does not increase
dopamine levels; furthermore, treating the mice with drugs related to
serotonin or norepinephrine did not ameliorate the disease's
symptoms. These results suggest that MDMA likely acts through a
pathway unrelated to these common neurotransmitters.

Future work will be required to understand how MDMA was able to
ameliorate the symptoms of Parkinson's in these mice and to assess
the toxicity of MDMA and related compounds in greater detail in the
future. However, this study opens the door to a search for compounds
related to ecstasy, which may provide a more effective treatment in
the later stages of the disease - and hopefully allow patients to
perform the simple functions of everyday life independently again.