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(23 Sep 97) Liquid Sinemet- Another 2c worth! Things are a bit slow this hot Tuesday morning, and since some of the correspondents seem confused, I'll add my bit to the ongoing discussion (without firsthand experience, just a lot of hearsay): 1. The purpose of Sinemet is to replenish dopamine that is needed to transmit signals across the gap between motor neurons of the basal ganglia. Dopamine replenishment is needed because the neurons that normally make their own have failed. When taken orally as the levodopa part of Sinemet, dopamine gets through the lining of the small intestine into the blood as levodopa, then into the brain where it turns into dopamine. Nobody has explained how this extra dopamine floating about in the brain replaces the very specific deficiency in the tiny gap between pairs of individual nerve endings, but Hey! It works! 2. Aside from the nagging suspicion among scientists that this extra dopamine over time may actually kill off more of the cells that are supposed to supply it naturally, in a vicious cycle of disease progression, there are three things to know about dosage: First, a too-high concentration in the blood (or brain) leads to excess movement, or dyskinesia. Second, a too-low concentration leads to immobility and muscle spasms, or dystonia. Third, the concentration of "extra" dopamine resulting from medication dissipates rather quickly; the higher the concentration, the faster it tapers off. 3. As most long-time PWP learn to their sorrow, the three factors above mean that if you take Sinemet periodically, in separate doses, you get a "sawtooth" effect: First a quick boost, then gradual decline, and finally the point where you need the next dose, and repeat the cycle. To avoid the unpleasant effects of too much or too little dopamine available at any given moment, you need to keep within the "comfort range" of concentration. 4. Several factors or strategies affect the concentration of dopamine and its variation with time: The more advanced stages of PD need more replenishment via medication, consequently with faster decline between separate doses. Sleep reduces the need for replenishment, physical or mental exertion increases it. The unwanted variation in available dopamine can be smoothed out by formulas (Sinemet CR) that simply dissolve more slowly, or by taking smaller doses at shorter intervals. But as the late Alan Bonander pointed out, in advanced PD the "window" between too much levodopa and too little gets smaller and smaller. When in advanced PD it no longer suffices to break the scored 25/100 tablets in half, taking the Sinemet as a drink permits smaller doses. Finally, the patient may resort to continuous infusion (into the small intestine, I think) by a battery-driven pump that is worn on a belt. 5. I have purposely omitted discussion of agonists, as that is a whole different ballpark; except to mention that you now see why drug makers eagerly pursue those agonists having more prolonged effect. Some are claimed to be needed only once a day. Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013