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hi stephan you wrote: >...About 50% of the newly diagnosed patients at first resist >levodopa therapy (me included). They are under the mistaken >impression (in my case gleaned from the several patient >authored books and pamphlets I read) that the effective >therapeutic life of levodopa is 5 to 10 years. The clinical >evidence is to the contrary. i wonder if the problem here is simply the wording in the books and pamphlets you mention maybe the description 'effective therapeutic life of levodopa' really should mean the 'honeymoon period' where tweaking and adjusting are not critical to preventing the 'on and off' phenomenon viz this description extracted from dr. kurth's press release on tolcapone: words in [] inserted by myself for clarity ----- Parkinson's is a brain disorder that affects about one in every 200 persons, most of them elderly. It is caused by degeneration of cells in the part of the brain (the basal ganglia) that regulates muscle tone with a nerve-signal transmitting a chemical called dopamine. Without this regulation, muscles become stiff, experience tremors, weakness, and slowed movement. Typically, the brain responds well to treatments with levodopa and symptoms are controlled, but this "honeymoon" period fades as the brain loses ability [as the disease progresses and more cells die?] to store levodopa and needs to draw more of the drug from the bloodstream. Doctors have been unable to figure out any way to deliver levodopa in consistent levels to the brain throughout the day, because it is so rapidly metabolized. The result is that many patients well along [5-10 years?] in the disease experience periods when their symptoms fade ['on'] and then slumps ['off'] in which their muscles become slow and rigid as the drug disappears. ----- re the 'honeymoon period' changing into a 'tweaking and adjusting' stage i've heard this progression referred to as the 'narrowing of the therapeutic window' where smaller doses are taken more frequently so as to avoid a roller coaster effect with the levodopa levels in my case i've made an adustment similar to the above, twice, once changing from 25/200 sinemet to 10/100 twice as often and once changing from 10/100 sinemet to 5/50 sinemet twice as often the first adjustment was about 5 years post dx and the second was 8 years post dx in effect, my sinemet level hasn't increased it has just become more fine tuned and 'smoother' for whatever it may be worth your cyber-sis janet janet [log in to unmask]