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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