On Sun 08 Jun, David Langridge wrote:
> BRIAN,IDA,AND OTHERS
>
> I have been so tied up in other matters in recent weeks that I have been
> unable to join in the latest spate of postings.
>
> However after a lot of experimenting with all sorts of schedules and doses I
> am sure that in my case the dyskinesia only comes to a small extent at the
> beginning of a dose of sinemet and almost always at the end WHATEVER THE
> SIZE OF THE DOSE.I have tried SinemetCR 25.100 one tablet at intervals from
> 2 to 4 hours - ok if there is sufficient overlapping but quite difficult to
> achieve in practice.CR 25.100 taking two tablets every 4 to 5 hours again
> the overlapping problem.Sinemet Plus 25.100 - quarter of a tablet every hour
> but this takes up to three hours to build up to give any effective relief
> and  tends to produce a strange sort of intermittent dyskinesia.  One third
> of the same tablet every hour produces a slightly better result.But here is
> the interesting thing on one occasion treating myself as a guinea pig I took
> one whole sinemetplus 25.100 tablet every hour for ten hours and the
> dyskinesia only started an hour or so after the end of the regime and more
> recently two 25.100 tablets every hour for 12 hours and again the dyskinesia
> not significantly unpleasant again came at end of dose. In both cases the
> higher doses produced a lot of energy and acted as an aphrodisiac.
> In addition to Seleginin 10mg I also take Permax 1mg a day and have tried
> more with no obvious benefit.
>
> These experiments with high and low sinemet inputs lead me to believe that
> end of dose dyskinesia is not just a simple matter of over dosing.Brian
> suggest that overdosing may have shot one into the 'twighlight zone'. It
> seems to me that that for people who suffer from end of dose there is a sort
> of very sensitive 'subliminal' zone on the way up to the fully dosed zone
> where problems occur with too low concentations of dopamine.If on starting
> your routine you are taking not enough sinemet you will climb too slowly
> through this subliminal zone and suffer start of dose dyskinesia but taking
> enough you will sail through it quickly and  provided you keep above it you
> will be ok until some time after your last dose which is not too bad
> depending on the rate you descend  back through the subliminal level.Best if
> this is when you are not  going to be very active.In practice this  is not
> very easy to achieve and it comes back to my original gripe several months
> ago that one ends up taking increased doses of sinemet not to deal with more
> severe pd symptoms but to deal with the dyskinesic effects of sinemet at the
> subliminal level. I would still prefer to use as little sinemet as possible
> and because of these effects I only really take it when I need it. For
> instance I usually go without medication until mid morning or when I am
> sedentary for long periods like driving a car  or sitting at this screen.
>
> All the best David 68/4
>
>
Hello to David, Ida, and Others, This debate is being carried out at
snail-mail speed, but perhaps this is appropriate, because we are all
feeling our way in the dark on this subject. I also am finding that
there are not enough hours in the day due to other committments.
   I have used the predictive side of my program to give me an
impression of what the various drug schedules would look like. I am
negotiating with Simon Cole to find a way to temporarily make sketches
viewable on a web site, rather than clog everyone's mail with my
diagrams.
   These plots are only estimates, because they use 'typical'
characteristics based on my and others data analysis but not,  of
course, your personal characteristics. It is interesting that you
chose 1 hour and 2 hours as your time interval, because that (again
assuming that the average data which I have used is representative)
results in a quite stable trace after the initial sorting-out at the
start.
  The 1/4 and 1/3 tablet data (How do you get 1/3 of a Sinemet tablet
?) , indicate levels of levodopa intake which approach my personal
requirement of 37.5 mg/hour of levodopa input, (Combined with 2.5 mg
of Permax (Pergolide). Note Permax takes no part in the little
scuffles as levodopa comes and goes: It seems to simply raise the
threshold of the mass of traces. You can then reduce your Sinemet
intake by that amount, thus gaining in margin.
   It is not clear to me from your post, whether you gained any relief
of symptoms from the 1/2 or 1/3 data. Did you get such a feeling?

   The 1 tablet per hour ,and the 2 tablets  per 2 hours result in the
same total input of a staggering 200 mg/hour. As the saying goes -
Boy, I couldn't live like that! I think that your ability to take that
level of input is due to a possibility that the majority of the drug
simply does not get to the brain, or alternatively it does get to the
brain, and is ineffective possibly because of your relative newness to
PD, I have doubts about the relevance of analysis done on people who
are only 1 to 5 or 6 years into PD.

    By the way, I was careful to emphasise that I have found out how
to get end-of-dose dyskinesia myself, and how to avoid it. I do not
have a clue about Why it happens, unless it is some sort of an over
spill condition, in which case my flooding river analogy may be
appropriate. Fortunately for my system, all of these 'Overdose'
conditions do not affect my analysis, because it stops short at the
first 'zero-condition' that it comes to.
  It's getting late, and I am not sure that I am making sense anymore,
so I will finish here. I believe it was you, David, who said that one
can get too involved in the detail, and we should spend more time
enjoying life. At 4 years into my PD, I would have agreed with you
whole-heartedly.  (I didn't write my program until I had had PD for 13
years.- simply because I didn't need it before then.

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