There have been several letters lately about putting off Sinemet therapy
until some unspecified later time. The reason usually given is that with time
Sinemet becomes progressively less effective in reducing PD symptoms. This is
true. The reason for this decrease in potency, however, comes not necessarily
from the use of the Sinemet itself, but rather from the progressive nature of
PD. My argument for this is as follows.
Our PD is caused by a progressive loss of dopamine producing cells in our
substantia nigra. By the time PD becomes clinically diagnosable, on the average
80% of the substantia nigra is gone. This is not a trivial loss. (Why Nature
has provided us with such a great excess or redundancy in substantia nigra
capacity is an interesting but unanswered question.)
As a result of this loss in dopamine-producing ability, PD initially
presents itself as a problem in SUPPLY. Sinemet supplies the brain with
additional l-dopa, the raw material for making dopamine. The effect is MAGIC!
Small doses of Sinemet can relieve the patient's symptoms to such an extent that
for a time they effectively disappear. All good things eventually run their
course and come to an end, unfortunately.
Not only does Sinemet now need to be administered in progressively larger
doses, but its effectiveness becomes less predictable, and the patient begins to
experience more sudden changes in the severity of his or her symptoms. This
on-off effect can be dramatic and very discouraging. (I am well into this stage
of PD.)
By this time the patient has very few healthy cells remaining in the
substantia nigra. Now it turns out that dopamine production was only ONE of TWO
important functions of the substantia nigra. It also is responsible for the
regulation of the supply of dopamine to the motor control centers in the brain.
This is all very reasonable. All production requires control.
The cells in the substantia nigra not only produce dopamine; they also
re-use it, store any excess in special internal vesicles, and maintain a sort of
internal audit of dopamine production, use, storage, and loss. In the absence
of cells capable of exercising these regulatory functions, the dopamine levels
in our brains are no longer subject to any local or internal control but now
depend on an external factor, the concentration of l-dopa in the bloodstream.
Succinctly put:
In its early stages, PD appears as a problem in SUPPLY; in its later stages, it
emerges as a problem in CONTROL.
Needless to say we as pill swallowers are absolutely incapable of
controlling the dopamine level in our brains with any precision whatsoever.
It is as if we were to try to control the flow and temperature of our
morning shower by adjusting gate valves at the city reservoir. Not only is our
valve control too crude to be effective, but every one else in the city is also
turning water on and off and the fire department is fighting several fires and
the water mains leak. We wrench our huge gate valves open and closed by
swallowing massive amounts of Sinemet which must then be digested and absorbed
into the bloodstream in competition with whatever else happens to be in our
intestines at the same time. The bloodstream carries the now much reduced load
of Sinemet (but still much more than the brain needs) to the brain with
who-knows-what kinds of loss along the way. There the brain selects a small
fraction of what is flowing by in the blood for absorption and use.
The brain has lost its internal dopamine control center (the substantia
nigra cells), however, and it has no natural backup system to turn to. Thus
Sinemet CR, disolving Sinemet in orange juice for sipping very small doses more
or less continually, pumps for injecting a Sinemet solution directly into the
gut, and other strategies for external regulation of the dopamine level in the
brain. Needless to say these are only partially effective.
The lack of live substantia nigra cells also restricts the amount of
dopamine which can be produced regardless of the l-dopa supply. It is for this
reason that substitute chemical neuro-transmitters (agonists) which will act
directly on nerve endings have been developed (Parlodel, Permax).
Anyway, that's the Andes theory of PD and Sinemet.
George Andes 62/14, and counting.
