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Dear Gerry, Barb Blake-Krebs and List, Let me start by stating how grateful to God I am that I was easily able to drive around today for 3 hours, from 11:40 through 2:55. IN CITY TRAFFIC, and on ice and slush and snow-covered streets, without a hitch. This is a definite IMPROVEMENT over a year ago. I began using Tasmar in late February, 1998, eleven months ago. I hope that Brig and Gerry may be encouraged to reconsider the idea of a new, but different, Tasmar trial period. I am in continuous conversation with my neurologist, John Boothby, M.D. about this slow, incremental method of starting Tasmar. I have had amazing results by SLOWLY increasing from 25 to 50 to 100 to 150 to 200 to 250 mg per full (24-hour) day, during the past 11 months on Tasmar. At 250 mg. / full day, and my SInemet+SinemtCR levodopa total now reduced from 1600 mg./full day to 850 mg./full day. I have almost no dyskinesia, except in the morning if I haven't had enough breakfast. I attribute any freezing up" primarily to the underlying PD disease process (akinesia or bradykinesia), in myself. If I were not on Tasmar + levodopa, I probably would be in horrible shape. My neurologist in Portland, although not a movement-disorder specialist, has practised for 25 or 30 years. We maintain a conversation that occurs, on average, once every two weeks. I have also maintianed regular office visits, about once every two to three months or so. Yesterday morning, he called me at home, and we talked for 25 minutes, with me on the speaker phone. We ended up realizing that patients AND doctors have a hard time figuring out Tasmar. But it can be mastered, and the slow, incremental dose method worked for me, including CUTTING PILLS in half to obtain 50 mg. doses. We talked about a radio program that could interact with the listening public. He asked me about the many List posts on Tasmar, as well as on the issues of liver function, and liver testing. My enzyme levels are wonderfully low, incidentally. I am building a Tasmar file-now almost 40 case history entries in it already. Ivan Suzman 49/39/36 On Thu, 21 Jan 1999 17:53:47 EST Barbara Blake-Krebs <[log in to unmask]> writes: >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>> > ^^^^^^ WARM GREETINGS FROM ^^^^^^^^^^^^ :-) Ivan Suzman 49/39/36 [log in to unmask] :-) Portland, Maine land of lighthouses 28 deg. F :-) ********************************************************************