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Gerry...You raise a good question when you ask what is in this drug to cause a patient to have increased rigidity/freezing when withdrawing the drug. I don't have the answer. Does anyone else? In order to try and better think about this, Gerry and all, I have engaged in a review exercise... What I know about Tasmar/Tolcopone is it is one of the newer treatments designed to increase the amount of levodopa (found in Sinemet) to enter the brain where it is converted into dopamine. If levodopa is taken by itself only 1% reaches the brain, as there are a whole array of natural enzymes in the body that treat levodopa as a "foreign invader" and rush to devour and expel it. So levodopa has some "guards" whose job it is to overcome these enzymes. What are these enzymes, and whose job is it to destroy*. ENZYME 1) Dopa decarboxylase - carbidopa allows 5-10 % of the levodopa to reach the brain. 2) MAO-B - Inhibitors - still more levodopa reaches the brain 3) Catechol-O-methyltransferase (COMT) - Entacapone and Tolcapone. Tolcopone is said to prolong the effectiveness of a single dose of levodopa by 70% **Entacapone acts mainly peripherally whereas tolcapone acts both peripherally and centrally. They induce a dose-dependent inhibition of COMT activity in erythrocytes and a significant decrease in the plasma levels of 3-O-methyldopa, indicating their effectiveness as COMT inhibitors. Consequently, they increase the elimination half-life of levodopa and thus prolong the availability of levodopa to the brain without significantly affecting the Cmax or tmax of levodopa. Clinically, the improved levodopa availability is seen as prolonged motor response to levodopa/DDC inhibitor and also as prolonged duration of dyskinesias in Parkinson's disease patients with end-of-dose fluctuations. The dyskinesias are managed by decreasing the daily levodopa dose in Parkinson's disease patients with end-of-dose fluctuations. Both pharmacokinetically and clinically the 200-mg dose of entacapone is the most effective dose compared with placebo. For tolcapone 100 and 200 mg have most often proved to be the optimal doses. Based on the duration of COMT inhibition entacapone is administered with each levodopa/DDC inhibitor dose whereas tolcapone is given three times daily. Both entacapone and tolcapone are well-tolerated. However, there seems to be a trend for tolcapone to induce more often diarrhoea and increase in liver transaminases compared with entacapone. Thus, COMT inhibitors are clinically significant and beneficial adjunct to levodopa therapy in Parkinson's disease patients with end-of-dose fluctuations. Their effects and significance also in the treatment of de novo patients need to be clarified. ------------------------------------------------------------------------ *Info derived from an article in local Parkinson Update, Spring 1998 **[Medline]J Neurol 1998 Nov;245(11 Suppl 3):P25-34 Department of Neurology, University of Turku, Finland. Abstract. PMID: 9808337, UI: 99023523 ----------------------------------------------------------------------- BTW, I am now going back on Tasmar, and am currently taking one in the evening. My experience this past month is the same as you observed in Brig--I slipped at least a notch or two below where I had been last March when I first started Tasmar...very unsettling. Best regards, Barbara Blake-Krebs in KS 58, 1984 [log in to unmask] In a message dated 1/20/99 6:16:44 AM, you wrote: <<Barb, Brig went on Tasmar as well, is just about off of it, but it has been sheer hell. Can anyone tell me why this drug seems to affect a lot of people this way when they try to taper off of it. What is in it to have brought this affect on so many patients? Brig had no freezing before, but now it's here. And I must admit, only because of a friend's advice, did he taper off as slowly as he did, we're talking a month of reducing dosage. I may be crazy, but it seems like tapering off of tasmar took him down a level or so. Gerry>>