Marge S. -
You asked about COMT inhibitors.
Levodopa is metabolized in the brain by an enzyme
called - catechol-o-methyl-transferase (COMT). The 'half-life'
of Levodopa is reduced by this enzyme in the bowel, the liver
and the brain [Levodopa usually enters the blood stream in
the bowel, then passes through the liver before passing the
blood-brain barrier]. COMT shortens the duration of each
dose of Levodopa.
Tolcapone ("Tasmar" - Hoffman LaRoche) and
Entacapone (Orion Pharma & Novartis) are COMT inhibitors
under FDA study. They are being studied in combination
with Sinemet only. Tolcapone blocks the action of COMT in
the intestines, the liver and brain and is beneficial in both the
early and late course of PD. Entacapone blocks the action
of COMT in the intestine and liver only (not the brain) and is
most effective in treating motor fluctuations in the later
course of PD.
More information will have to await the FDA studies.
On the other hand, a dopamine agonist directly
stimulates the brain's dopamine receptors (D1, D2, etc.) by
mimicking the effect of natural dopamine. Therefore they do
not require the remaining dopamine neurons to make
dopamine. Apomorphine was the first known agonist.
An agonist continues to work in late stage PD because it
does not require the processing of dopamine neurons.
However, no agonist can stimulate the receptors like
dopamine can. Scientists believe that an agonist doesn't
quite bind to each receptor as well as dopamine and hence
the side effects (dyskinesias) result from oversensitivity of
the receptors.
As you can see, these are two different approaches to
overcoming the problem of reduced dopamine in our brains.
Stephan 53/7
