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Sinemet and Fatigue (20 Mar 1997) Of possible interest to others on this list, I'd like to share this recent experience, and ask if anyone else has had it too: In my (fairly) early stage of PD, I now take the equivalent of half a 25/100 Sinemet every 3 hours or so (depending on how soundly I sleep at night). The "end-of-dose" warning comes in the form of fatigue and depression. Partly to keep in shape, I still do yard work, with a shovel, lugging heavy stuff, etc. I notice that any concentrated effort, either physical or mental, seems to increase the need for Sinemet. After about a half hour of work, whether it's physical labor or just doing the daily crossword, I start getting back pain, always in the upper thoracic area but not always the same exact spot. I might otherwise ignore the fatigue and just keep on working, but the pain quickly intensifies until I must lie down. After a few minutes I'm fine again. Advancing the Sinemet schedule does the same thing. It "kicks in" in 15 to 20 minutes, sometimes sooner. If I take it easy for a day or so, I can resume the usual 3-hour interval. This tells me that in addition to the steady depletion of dopamine in the body, there is some kind of storage site where a basic level needs to be maintained. When you start withdrawing your "principal" faster than the rate of replenishment, you soon get in trouble. It also tells me that dopamine affects muscles. Normal fatigue is accompanied by pain, because muscles can't get rid of lactic acid, or whatever it is, fast enough, and dopamine helps them do that. I've written here before about the urgent need for more info about how dopamine acts 'outside' of the central nervous system, and this experience seems to emphasize that point. Comment, anyone? Cheers, Joe J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks CA 91403