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Hello everyone The main body of this post is a repeat of an exchange of views which I had with Bob & Joy Graham a couple of days ago. Looking back on it, I thought that the range of subjects, and the interesting points which were raised by them warranted a larger audience. I hope you agree. Regards, Brian Collins =========================================================================== On Thu 02 Jan, Bob & Joy Graham wrote: > Hello from stinking hot Australia where we are in our second day of the new > year and it is looking like being 42C again. > > I enjoyed reading your recent post about taking levodopa, and the option to > take it in small quantities. Of course, this is one recognised theory and > that is why many advocate the slow release forms such as Sinemet CR and > Madopar HBS The sort of Controlled Release tablet which I am talking about for a newly- diagnosed PWP would release about 10 mg/hour over a period which could be anything you like, depending more on the ability of the tablet manufacturer to turn out a regular release rate. In fact there should be a range of such tablets, all lasting the same time, but each one having a pre-set release rate, ranging from 10mg/hour up to about 100 mg/hour. My ideal tablets would cover the range 10 mg/hr to 100 mg/hr in increments of 10 and 1 mg/hr to 9 mg/hr in increments of 1. You could then match anyone's requirement precisely. If you take my case as it is right now, I take 1 and a half Madopar dispersibles every 2 hours : That is 37.5 mg/hour. If my intake falls below about 32 mg/hr I switch off, and if it goes above 42 mg/hr I get dyskinesias (These figures were obtained with the help of my analysis program). There was a time when the rate of release which I could tolerate was high enough to allow me to use the standard controlled release tablets, which was great, but I can't take them now. ( Note that I said 'tolerate' not 'need' : that has for a long time been 37.5 mg/hr). >- but sadly, I understand that one has to take more of the > levodopa to get the same response, and this is problematic. I assume that you are referring to the 'Bio-availability' of the CR tablet. I am far from convinced that such a thing exists: my program matches the perceived output with the milligram content of the CR tablet without the need of a factor on the effective size of the tablet. As I understand the argument, less levodopa arrives at the brain because , since the tablet contents have been 'in transit' for a longer period of time, the chemicals trying to attack the levodopa are more likely to succeed. On the other hand, I suspect that a much more significant feature is the amount of protective carbidopa available to shield the levodopa from this attack. Either way, I don't see why it should be 'problematic': you just take a bit more levodopa to compensate. > Bob and I were curious that whilst you recommend breaking the tablets up, > and taking small amounts more frequently, you didn't recommend making > liquid sinemet. Have you done this yourself? Have you found that it > doesn't work for you? I certainly think it is useful for those having > dyskinesias and a small "therapeutic window" after many years of treatment. Theoretically I would agree with you: you can in principle tailor your drink to any value of concentration you like. in fact, if you read my program description on Ron Vetters web site, you will see that I suggest doing just that. But (and it is a big but), since I wrote that, I have seen the effect of liquid Sinemet in data sent to me for my program from a man who uses it. The effective characteristic is one where the speed of uptake (i.e. the time from drinking the mixture to the time for the effect to be felt) is amazingly short. The bad news is that having dumped all its levodopa in record time, the output rate fades back to zero at equal speed, which is the last thing that we want. This man was having to cope with effectively a sine wave, alternating from full on to full off at a rate of 2 cycles per hour ! That is the last thing I want > Another point: > We here in Aust are able to use Motilium/Domperidone which is the only anti > nausea drug which does not (ultimately) produce drug-induced PD symptoms. > Is it available in the UK? > We noted in the APDA mag. recently that whilst it was not available in the > USA, a neurologist was telling patients to contact him for an address of a > pharmacy in Canada which would supply it. The same doctor said that he had > noticed more nausea with the Sinemet CR. Is this your experience? This is interesting - are you saying that Motilium can be used to enable PWPs who suffer nausea when taking levodopa, to overcome the problem? If this is known over here, I am not aware of it. I will make some enquiries. I am not aware of any evidence that suggests that CR tablets provoke more nausea. > Do you know anyone who has tried the levodopa patch? It seems to me that > this could be a great solution, since one can simply remove it when one is > getting overdosed, i.e. dyskinetic. (It wouldn't work for those with > sensitive skins, I know). I think that if you read the small print you will find that the statements do not actually state that the patches contain levodopa. I suspect that they will contain one of the new dopamine agonists, and thus will still require levodopa to be taken as well. > i am curious that in your general advise, you don't comment on the action > of Deprenyl which elevates dopamine concentrations by blocking its > breakdown, and therefore enabling a person to take less l-dopa. Are people > in the UK still anti-deprenyl? There are two articles in the recent NPF > magazine (do you get these -- if you don't I thorougly recommend them) > which seem to refute the "infamous" UK study which slammed deprenyl, and > prove it was ill advised, or at least too hasty. You are making a lot of claims in the above paragraph. This is how I see it: Deprenyl (We usually call it selegiline) works by blocking the action of MAO -B, which normally attacks and breaks down dopamine. So the hope is that a bit more dopamine will be left to prolong the effective duration of a tablet. Why bother? I can get the same effect either by taking a bigger tablet, or bringing forward the next tablet. And what are you getting for your stretched timescale? - your MAO-B ratios are all mixed up, you have got a compound in your brain which produces Amphetamine as it breaks down ( That's why you have to avoid taking the deprenyl near bedtime - The dreams are unforgettable. Yes, I've been there, and I took myself off selegiline. My rule is basically : The neuros can play with my brain, but my mind is mine and hands off! These are dangerous chemicals which we are playing with- Selegiline + Demerol can Kill you. My attitude to anti-cholinergic drugs is thw same- acetylcholine is there in your brain for a reason, and screwing about with the proportions, in the hope that it will allow a bit more dopamine to be produced seems crazy to me. By the way, I have never accepted the story which came out of the UK about Deprenyl, just as I never accepted the results of the tests which said it was a good thing in the first place. -- Brian Collins <[log in to unmask]>