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Whether motor fluctuations and dyskinesias are more related to duration of levodopa treatment or to duration of Parkinson disease (PD) has been debated since their recognition shortly after levodopa was introduced in the 1960s. The shortening of response to levodopa (“wearing off” effect), which often precedes other levodopa-related motor complications, has been attributed primarily to shortening of levodopa's half-life in the striatum, without a measurable change in the peripheral pharmacokinetics. Thus, as a result of loss of striatal dopaminergic terminals, the brain's ability to store and buffer the shifts in striatal concentration of levodopa is lost. Now, a PET study provides further support for this presynaptic theory.
In 36 patients …