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]>