Hi, Here is part 4 of Living with Levodopa
TABLE 1
The Main Forms of Sinemet and Madopar Tablets
_________________________________________________________________
| Carbidopa Benserazide Sinemet Madopar |
| Quantity Quantity Name * Name * |
|_________________________________________________________________|
| 250 mg 25 mg Sinemet 275 --- |
| |
| 100 mg 10 mg Sinemet 110 --- |
| |
| 100 mg 25 mg Sinemet PLUS --- |
| |
| 50 mg 12.5 mg Sinemet LS --- |
| |
| 100 mg 25 mg Sinemet CR 125 |
| |
| 200 mg 50 mg Sinemet CR 250 |
| |
| 200 mg 50 mg --- Madopar 250 |
| |
| 100 mg 25 mg --- Madopar 125 |
| |
| 100 mg 25 mg --- Madopar CR |
| |
| 50 mg 12.5mg --- Madopar 62.5 |
| Dispersible # |
| |
| 100mg 25 mg --- Madopar 125 |
| Dispersible # |
|_________________________________________________________________|
* These names may be valid in the UK only
# Water soluble tablets
APPENDIX 1
Tablet Composition, and the Reasons Why.
Dopamine itself is unable to pass through the blood/brain barrier- indeed,
this is an essential part of the way the body works. In the body, Dopamine
acts as a hormone, where one of its main functions is to control the blood
flow throughout the body. In the brain, Dopamine is produced in the
Substantia Nigra, and acts as a neuro-transmitter. These two systems are
totally separate: The only reason that we need to consider the Dopamine in
the body is that we have to smuggle the tablet-form of Dopamine through the
body to get to the brain. The first problem, as mentioned above, is that
the Dopamine molecule is too large to pass through the blood/brain barrier.
The great breakthrough came when it was realised that the precursor of
Dopamine (Called levodopa) would pass through the Blood/Brain barrier. (a
precursor is that chemical which is one reaction away from the final
product). In this case, levodopa is able to pass through the Blood/Brain
barrier. Once through the barrier, there is an ample supply of the enzyme
dopa decarboxylase to promote the final transformation of levodopa into
Dopamine. There was one problem: The enzyme dopa decarboxylase is also
present in considerable numbers in the body, and during the time it took
for the levodopa to travel to the brain, the levodopa was subject to
continuous attack. The result was that less than 1% of the levodopa
survived the journey - the rest was converted into Dopaminein the body.
All that extra Dopamine caused severe problems in the body, leading to
fluctuating heart beat, tiredness, and nausea. The solution to all those
problems was found in Carbidopa, which is an effective dopa decarboxylase
inhibitor. Thus the levodopa is protected from attack in the bloodstream,
and, as an extra bonus, the carbidopa is stripped off when the combined
molecule comes to the Blood/Brain barrier. A similar effect is achieved
in the Madopar tablet by using a chemical called Benserazide.
===========
APPENDIX 2 - Finding the Optimum Dosage of Levodopa.
This is going to be difficult: I am trying to describe how to do by hand,
a job that really requires the use of my Analsis Program for precise
setting.
I first want to explain that the charts, graphs etc form part of a
coherent model which I have concocted to model the brain's reaction to
levadopa, and dopamine agonists. I am quite prepared to be told that it
doesn't work like that in reality: I only claim that this model reacts
sensibly to inputs, and generates outputs similar to real life.
The first thing to do is define a variable which we can use to tell the
System whether the subject's condition is overdosed, underdosed, or
properly medicated, and points in between. This highly subjective way of
working is the only way that I have found which gives the necessary
precision and resolution which I have found to be necessary.
Consider a trace of what happens to the concentration of levodopa in
the bloodstream after the subject has taken a tablet of Sinemet (This
plot is relevant only because it is the nearest that researchers can get
to measure what is going on in the brain itself, and even there the
measurements can be misleading).
The trace has four separate sections, which are discussed below:
1/ The delay after the tablet is swallowed, before the levodopa reaches
the brain. This is a function of the efficiency of the digestive system,
and the speed of transmission through the small intestine into the blood
stream.
2/ The initial rise from zero to a peak value. The shape of this line is
determined by the same parameters which affect item 1/
3/ A period where the concentration of levodopa rounds out and starts to
decay , eventually reaching zero. This decay characteristic will be
affected by the attack in the bloodstream on the Levodopa/Carbidopa
compound, and in the brain by the rate of attrition of the Dopamine as it
is decomposed and returned to its basic components.
These phases of operation can be expressed as functions of the rate of
flow of levodopa, rather than concentration of levodopa, because there is
a direct relationship between them. The only problem is that if we chart
the subjective condition of the subject, we find that in between the
rising input line, and the falling tail-end trace, there is a period of
operation where the 'comfort level' of the patient is apparently constant.
I now believe that the constant value of the mid-term period is brought
about by the trimming function of the dopamine production site. In other
words, the rate of input of of levodopa may jump around, but the smoothing
effect of the brain's dopamine producing center ensures that whern it is
possible, The brain manages to carry on smoothly at the optimum flow rate.
There is further discussion in Appendix 3, (an article which I have
published previously as 'CHART A'). However, Appendix 3 contains a GIF
chart /picture attached to it, and will clog the works of a text-only
internet system. For this reason, I will transmit Appendix 3 only to
those who request it.
--
Brian Collins <[log in to unmask]>
