On Tue 07 Jan, W.S. wrote:
> I am a new member to your group, I am looking
> for information on parkinsons for my mother, I am interested
> in the ups and downs of sinemet cr, could anyone tell me what
> the usual dose of sinemet cr is ? just for comparison, we are
> not changing it without the doctor's say so...
>
> I have gained a lot of helpfull information from this
> group in my first 24 hours, I thank you all,I am in the prosess
> of changing doctors, we need more info than " take 2 sinemet and
> see you in three months" It is good to see such an active group
> sharing information, and it is helpfull to know the symptoms that
> are parkinsons and not unusual. If I am actualy sending out this
> message, like I think I am, ( I'm new to computers and Internet)
> I wish you all well, and thank you for your help.
> [log in to unmask]
>
>
Hello W.S. You are very sensible to try to find out the principles which
determine how and why we take Sinemet. I will try to give you the story
in a compact form, but it is quite complex, so I may have to do it in
installments.
1) What is Sinemet
Let's clear away one point; Sinemet is a brand name for a tablet
containing levodopa and carbidopa. In the USA there are no alternatives
so Sinemet has become the standard name. In many other parts of the
world there is an alternative, called Madopar, which is functionally
interchangeable with Sinemet. The key compound in both these tablets
is levodopa ( or L-dopa ), which is the pre-cursor of Dopamine, a
neuro-transmitter. (Pre-cursor means that it is only one chemical
reaction away from dopamine. The brain uses dopamine in the process of
sending messages from the brain to the muscles of the body. In the
Parkinson's sufferers brain, the part which is responsible for
production of Dopamine - the substantia nigra - for some unknown reason
progressively dies off, and when approximately 80% of the normal
complement of dopamine-producing cells have died off, the familiar
tremor and/or muscular rigidity begins to reveal itself, along with an
assorted bunch of other symptoms.
2) How do we get the levodopa to the brain?
It is not as simple as taking a tablet of levodopa, unfortunately.
When we take a tablet like this, it goes through a pretty wild ride
before it finally gets to the brain. First it has to survive until
it reaches the lower intestine, where it is absorbed through the
lining of the lower intestine (Providing the last meal is not blocking
the way). From there it has to hitch a ride in the blood stream,
until it finally arrives at the blood-brain barrier (The BBB). It
then has to cross this barrier, get to the substantia nigra, and
make up for the missing cells.
In the blood stream, there are many chemicals whose sole function
is to break down Large Amino Acids of which levodopa is one. If we
swallowed say 200 mg of levodopa, less than 1mg would survive the
journey to the brain. This is where the carbidopa comes in (In the
madopar tablet the other constituent is Benserazide, but it does just
the same job as carbidopa). The carbidopa protects the levodopa during
its journey to the BBB. Now comes the clever bit: the BBB is very
selective about what it will allow through to the brain. It will not
allow dopamine, or levadopa+carbidopa, or carbidopa for instance.
However, it will allow levodopa by itself, and in the process the
carbidopa is stripped away from the levodopa, and left behind.
So far so good, but the brain itself is full of chemicals just
waiting to pounce on the levodopa, break it down to its constituents
and cart it away. A small quantity makes it through to the substantia
nigra, where it performs its neuro transmitter role, before being
pounced on and etc, etc.
One last pitfall to be avoided: If we supply too much levodopa, the
effect is as if the dopamine overflows the assigned neural pathways, and
'floods' the system surrounding it. This causes muscles at virtually
any part of the body, depending where the spill occurs, to initiate
muscular movement which we did not command. These uncommanded movements
are called dyskinesias, and they can be as bad or worse than the PD
tremor.
3) You may begin to see that what we have to do, is by trial and error,
find a tablet which will deliver enough dopamine to supply the
brain's requirements, and allow for all the losses along the way.
What this boils down to is that we are trying to maintain a constant
RATE of FLOW of levodopa, through the day. If we let the flow rate fall
too low we get PD tremor etc, and if we get the rate too high, we get
Dyskinesias.
I have gone far enough for one day. In the next part, I will try to show
how a newcomer can tolerate rates of flow ranging from (Approximately)
10 mg/hour up to 100 mg/hour, while an old hand like me, after 17 years
of taking Sinemet/Madopar can only tolerate rates of flow ranging from
(about) 35 mg/hour to 40 mg/hour.
Regards, Brian Collins
--
Brian Collins <[log in to unmask]>
