On Tue 10 Dec, John Lochore wrote:
> It was fascinating to read Brian Collins' note about carbidopa, and the postulated act
> ivity of the excess carbidopa being let loose contributing to fatigue, etc.
>
> In our household we have the "other" levadopa source - not Sinemet, but Madopar. Inste
> ad of including carbidopa, it has as a partner another substance called Benserazide. I
> n our tablets the proportion is half that of the l-dopa.
>
> Might it be expected that the same effect could result from excess benserazide as from
>  excess carbidopa? And if so, at what threshold level would an effect be suspected?
>
> Is there a Madopar product that contains a proportionally lower ratio of benserazide t
> o l-dopa?
>
> Robyn & John Lochore
>         Perth, Western Australia
>
Hello Robyn & John thanks for your comments.  I'm not too sure which note of
mine you are reading, so I enclose a copy of a note which I wrote, in which
you will see that I have covered the subject of Benserazide vs Carbidopa, and
very interesting it is too. I didn't realise that you could get Madopar in
Australia; that makes Canada, UK and Australia at least where there is a choice of Sinemet or Madopar. It might be worth a survey to see if any Madopar takers
have the lethargy symptoms. (I suspect that they may not. We could use the
Sinemet takers as reference. I think I will start the ball rolling within the
next day or two.
Regards,
--
Brian Collins  <[log in to unmask]>
 ========================================================================Date: Sun, 24 NOV 1996 23:41:28 +0000 (GMT)
From: Brian Collins <[log in to unmask]>
Subject: Carbidopa toxicity
To:
    Parkinson's Disease - Information Exchange Network <[log in to unmask]>

Subject: Carbidopa Toxicity

Hello to you all, and thanks to Pam Barnett for her kind comments.
I must apologise for not responding to any discussions
over the last week. I have been up-grading my computer with a super-fast
new processor, and it took a little while to teach it who was in charge.

Anyway, I am back now, and would like to address some of the points made
regarding Carbidopa. I do believe that too much Carbidopa can be bad for
you. The story as I understand it is:

1/ The function of Carbidopa in the Sinemet tablet is to protect the
Levodopa from chemical attack as it travels in the blood-stream from the
lower intestine to the Brain. It first cane to my attention that there can
be such a thing as too much Carbidopa when reading the excellent book by
Dwight C. McGoon- 'The Parkinson's Handbook' (Published by the Norton Press
of New York) - I will say a little more about this book later-. Since then
I have asked several neurologists the same question, and the concensus is
that only 70 to 100 mg of Carbidopa per day is required to provide effective
protection to the levodopa.

2/ So: What happens to the unwanted excess carbidopa. The clever thing about
Carbidopa is that it cannot get into brain, and is forcibly separated from
the levodopa at the blood-brain-barrier. By this time, the Carbidopa, cast
adrift after doing a fine bodyguard job on the levodopa, is probably going
to have what we might call an attitude problem, so it sets off to do the
one thing it is good at: protect Large Amino-Acids from chemical attack.
And they are there in profusion; their reason for being there to act as the
building blocks for protein in various parts of the body.They need to
interact chemically to do their job, and the carbidopa will spoil this
delicate balance, until it is eventually broken down by the liver. The
theory ( Idon't think it can be called more than that) is that by
interfering with the delicate balance in the blood stream, the Carbidopa
produces feelings of lethargy, sleepiness, lassitude,  etc.

3/ If the above argument is unconvincing to a sceptical neurologist or
doctor, you might ask why else do Sinemet produce a specially low dose
tablet having  100 mh of levodopa and only 10 mg of Carbidopa.

4/ This next point may be a complete red-herring, but I just put it forward
as a possibility.  A friend of mine living in Derby is, as far as I know,
the record holder for levlodopa usage: taking an average of 3000 mg of
levodopa per day. - That's right: Three Thousand milli grammes per day.
(And of course 750 mg of Carbidopa ). I remembered him describing symptoms
very like those listed above, and before writing this email, I phoned to
check his status. When I listed the symptoms he immediately agreed that
they were a perfect description of his condition, but then said that he no
longer has the problem, since he switched to Madopar! ( For the benefit of
USA residents, I should explain that Madopar is available in many countries
as an alternative to Sinemet, and it functions interchangeably with
Sinemet in normal useage.)  Where Sinemet contains levodopa and carbidopa,
Madopar contains levodopa and Benserazide. I don't know enough chemistry
to have a clue as to whether this is significant, but it does make you
wonder.

To return to Dr. McGoon's book. The first 50 or so pages contain by far the
most clearly-written and jargon-free description of how the parts of the
brain which are associated with PD work, and I would recommend it to anyone.
However, when he gets on to the 'Drug Holiday' idea, I switch off! I have
occasionally (for quite unrelated reasons) found it necessary to go without
my tablets for a day, and I would say that the relief when the first dose of
levodopa cut in after that ordeal was great (in comparison with the
preceeding 24 hours). but I don't think it went beyond that.
    I do recognise however that perhaps the point at which I am in the long
decline that we call PD may be different to Dr. McGoon's  point. We all tend
to see things as they affect us personally, and Parkinson's being what it
is, with the variety of effects being almost as numerous as the number of
sufferers, I may yet find myself agreeing with the idea of a 'drug holiday'

I would be interested tp hear from anyone with experience of both Madopar
and Sinemet, especially if one or the other produced different reactions
in the patient.

Regards
--
Brian Collins  <[log in to unmask]>
 ==========================================================================