Listmembers,

About Remacemide:

Janet Patterson searched in the archives for remacemide and the last
message she found said:
"NEWS-New drug-REMACEMIDE-safe...but not effective by itself".

This is true, but nevertheless it might be an important med. for PWP’s that
suffer from end of dose dyskinesia. I paid attention to it because
remacemide is an anti-glutamate and I have a special relation with
anti-glutamates.,  To explain that I must repeat a story that I wrote before.

I  suffered from end of dose symptoms soon after I had started to take
levo-dopa. These symptoms consisted of a dystonic tremor and  feeling
agitated, being not able to stay  seated. They showed up when the levo-dopa
was wearing off. It was confusing because the motor agitaion was supposed
to be  a "top of meds" symptom. Wen a friend, who had been an alcoholic,
visited us and saw
me  with those "wearing-off" symptoms, he told me that he recognised them,
being like the symptoms he thought were the worst that happened to him in
his alcoholic past. The dystonic tremor and the agitation, having to walk
up and down his room, he recognized as a bad memory when awakening a few
hours after heavy drinking.
Some time after that I was, at the Rotterdam Central Station, accidentaly
together with a group of junks. l couldn’t stop staring at one of them, who
was in need his next shot. I was struck by the resemblance of his state
with mine, when in need for my next dose. So I started to call these states
"my cold turkey" and didn’t think it was something important, but when my
cold turkeys grew heavier and the tremor was replaced by a dyskinesia, that
was really tormenting and could not be controlled, I thought that may be
the fact of the resemblance with the junk was not an accidental one, but
meant that there was a common cause and a common cure.
So I started looking for meds that were used in detoxification of addicts.
I got a tip on the French Parkinson list, which said that anti-glutamates
were thought to be able to do the trick of both being helpful to addicts
with abstinence symptoms and with levo-dopa induced  ‘wearing of dyskinesia".
I started looking for info about anti-glutamates, but didn’t find much. In
stead of anti-glutamates I got a pallidotomy and  because of the miraculous
results as far as dyskinesia was concerned, I did lose much interest; but
then the growing dyskinesia in my untreated side let my interest grow again.
And now I found  much more  literature about it. But although experiments
with existing anti-glutamates as rilutek (slows down the progression of
ALS) and dextrometorphan (used as a substitute fot codaine in over the
counter cough syrop and pills) claimed positive results, they were not a
focus of much attention. But in the more general literature on parkinson
research the subject of anti-glutamates was increasingly showing up.

Especially in Tuebingen in Germany and in the UK ( Manchester and
Birmingham) much research is going on with the intention to develop such a
med, an anti-glutamate med that prevents dyskinesia. The anti-glutamates
that were actually produced, like rilutek (slows the progression of ALS)
and dextrometorphan, were also tested for their effect on levo-dopa induced
dyskinesia, but while reports about these tests were frequently found in
litterature, they didn’t show up in the mainstraim journals and were
neither figuring anywere as Big News, unlike the article about remacemide
just now.

The role of glutamates  in Parkinson’s disease itself and in the extent of
its symptoms is thought to be, that the excitary effects of glutamates are
not adequately inhibited anymore when the supply of dopamine is limited.
Too much glutamate has effect on the symptoms. It is the determinant of the
hyperactivity in the globus pallidus and the subthalamic nucleus and that
causes the levadopa-induced dyskinesia. The theoretically successfull use
of anti-glutamates has been called a "chemical pallidotomy". But too much
glutamates also has a role in the cell death that causes the progression of
the desease by producing, so is said, too high a level of intra-cell calcium.

Comparing the approach in Germany with the one in the UK, it seems that the
Germans are more easily satisfied with the criteria to develope medicins
and have in fact produced some.
The British seem to need more fundamental research before they start
developing medicins.
So, if the German antiglutamates don’t do the job we’ll just have to wait
for the one’s from Birmingham or Manchester. But I might be mistaken.

Ida Kamphuis .

Literature: only a small, and not meant to be representative, selection.

First a Quote from the homepage of  Jon Brotchie from the Victoria
University of Manchester:

START QUOTE:
"In recent years our work investigating the mechanisms  by which
neurotransmittters within the basal ganglia interact with each other  has
allowed us  to propose and demonstrate, to varying degrees,the
anti-parkinsonian and anti-dyskinetic eficacy  of, glutamate antagonists,
kappa antoganists, cannaboid antagonists, 5-HT antagonists, opioid
antagonists, a2 antagonists

In several instances these concepts have now moved toward being tested in
clinical trials.

We will continue to develop novel ideas  derived from our studies on the
basic sientific issues relating to signal transduction in the basal
ganglia. Our more recent work has begun to throw light on the functional
role played by:cholinergic receptors , tachykinin receptors, metabotropic
glutamate receptors  and nitric oxide.in the complex interactions
underlying the control of movement and generation of movement disorders
within the basal ganglia and unravel the complex interactions underlying
cell-cell signaling in these regions. The practical  implications of our
work will remain
to: define novel non-dopaminergic treatments for Parkinsons disease and to
define adjuncts to current dopamine-replacing therapies  that will reduce
the incidene of treatment- related dyskinesias.
END QUOTE.

Hoffman PL
Glutamate receptors in alcohol withdrawal-induced neurotoxicity
Metab. Brain Dis. 1995 Mar;10(1): 73-79
PMID:7596330; UI: 95319395

Acamprosate, a novel anti-craving compound acts via glutamatergic pathways
Walter Zieglansberger :M.D. Ph D
Max Planck- institute of psychiatry, Munich, Germany

Scmidt  W.J.
(1997) Zur Neurobiologie von Suchterkrankungen  ( To a neurobiology of
addiction)
Nervenheilkunde, 16, 197-200.

Schmidt W.J. & Kretchmer  B.D.
(1997  Behavioral  pharmacology of  glutamate receptors in the basal ganglia.
Neurosc. Biobehav. Rev., 21, 381-392.

Montastruc JL. Rascol O Senard JM.
Service  de Pharmaclogie Clinique, Inserm U 317,
Faculte de Medicine Toulouse, France
Glutamate antagonists  and Parkinson’s disease: a review of clinical data
PM 195605.

Neurosci Biobehav. Rev 1997 Jul:21(4) 447-53
Blanchet P, Papa SM, Metman LV, Mouradian MM, Chase TN
Expermental Therapeutics Branch, National Institute od Neurological
Disorders and Stroke, Bethesda MD 20892-1406 USA
Modulation of levodopa induced  moter respose complications by NMDA
antagonists  in Parkinsons disease

Amino Acids 1998; 14 (1-3): 75 -82
Blockade of glutamatergic transmission as treatment  for dyskinesias and
motor fluctuations in Parkisons disease
Verhagen Metman L, Del Dotto P, Blanchet P.J., van den Munckhof P, Chase TN


Kind regards / Vriendelijke groeten

Ida Kamphuis