Hello W.S. Here goes with part 2 of my explanation of the ins and outs of taking Sinemet. I have probably given you quite a shock at the complexity of the subject, but if you save these notes I feel sure that the day will come when you need to know some aspect which is covered in here. The=20 reason why I am going into this in such detail is that I have not seen all the points pulled together in one article before. 4) Getting the best out of your Sinemet tablets with almost any ordinary tablet, we are accustomed to a relaxed sort of regime such as 'Take one before meals', or 'Take two per day',etc It is obvious that it is not important that the tablets be taken at a specific time or in a specific order. Sinemet is different, because we=A0are trying to maintain the rate of flow of levodopa reaching the subsrantia nigra. A question which occurs to me at this point is : If flow rate is so important, how do we manage with effectivly three sizes of tablet: 50mg, 100mg, and 250mg ? True, you can break them=20 in half but the=A0steps are still large. The answer lies in the ability of the brain to regulate the=20 production of dopamine so that in a normal person, the dopamine is produced and sent to the required site at the right time, and in the right quantity. The normal brain has a substantial over-supply of dopamine-producing cells, so that about 80% to 90% of the production capability has to be lost before PD symptoms become visible. I should say that the description of the system which follows is my own, but aside from probably being rather over-simplified, I am convinced that it accurately describes the levodopa system =20 It is reasonable to assume that even in a non-PD person, the normal production rate of dopamine is just above 10% of the maximum. (corresponding to the 90% of cell loss required before the PD symptoms start.=20 It is also reasonable to assume that if the production rate should rise above this normal level by a quite small amount, then we are in dyskinesia country. Similarly if the flow rate falls below the=20 10% level, the PD 'Off' condition starts up : Tremor, rigidity etc. When a lump of Sinemet appears in the brain, the automatic system detects this intrusion, and makes room for it by throttling back the natural dopamine production rate. When a person has just been=20 diagnosed as having PD, their production capability is of course 10% of the maximum. The brain therefore has the capability to make room for a quite large quantity of external levodopa, typically 300 mg or more. As PD proceeds, the quantity of dopamine-producing cells continues to decrease, and inevitably so does the amount of Sinemet which can=20 be tolerated, so that as time goes by, it becomes more and more=20 difficult to achieve an exact match of the required dopamine, and over- or under-dosing results. This aspect of the dopamine regulation system is covered in a more understandable way, in 2 charts (A and B) which I have distributed before. If any newcomers are interested, they can email me, and I will send them a set. For the newly-diagnosed PWP, when they are finally introduced to levodopa, they are typically prescribed a large tablet, say 250mg, which will last anything up to 5 or 6 hours. This is accepted by the brain as described above, but in reality, we could also have achieved an acceptable treatment by taking a tablet which released a mere=20 10 mg per hour. Unfortunately such a tablet does not exist.=20 5) Controlled Release tablets or Standard The controlled release tablet is designed to release its load of levodopa over a period of time, thus avoiding the chance of a sharp=20 increase in flow occuring shortly after the tablet enters the=20 bloodstream. Typically a standard tablet, such as Sinemet 25/100=20 (100mg of levodopa) will last 2 to 3 hours, thus giving a rate of 50mg/hr to 33mg/hr. The CR tablet contains 200 mg of levodopa and, since it lasts about twice as long, gives the same nominal rate, and of course is more convenient. I took the CR tablets when they first became available, and for 2 or 3 years, they were ideal. If newer users find that they can get a satisfactory response, then I would recommend their use. In my case, my tolerance level fell below 50mg/hr, and I could not tolerate the quantity of levodopa released by the CR tablets. You should be very clear about this: The continuing reduction in the tolerance level is Not due to the=20 way that you took the tablets; it is due to the continuing erosion of the cells in the substantia nigra. When you start on Sinemet, you have several years of virtual freedom from the symptoms of PD. Enjoy it, its free. You are not=20 mortgaging the future, Not only that, nono of the other drugs can give that degree of control. Eventually, you will need to resort to combinations of these drugs, but that is another story. =20 I hope that some of you have managed to follow me through to the=20 end. If you have, I hope you feel that perhaps some of the mystery has been drawn aside, and you know what you are dealing with. =20 Regards, =20 --=20 Brian Collins <[log in to unmask]>