RELATIONSHIP BETWEEN LEVODOPA CONCENTRATION, DYSKINESIAS, AND MOTOR EFFECT IN PARKINSONIAN-PATIENTS - A 3-YEAR FOLLOW-UP-STUDY

We conducted a 3-year prospective assessment of the relationship betwe en levodopa (L-DOPA) plasma concentration and both dyskinesias and tap ping motor response after a standard oral L-DOPA dose in II parkinsoni an patients, Hoehn & Yahr (H & Y) stages 2-3, with L-DOPA therapeutic response complicated by involuntary movements. Over the 3-year period, duration of the tapping effect significantly decreased, while that of dyskinesias showed minor changes. Initially, the L-DOPA therapeutic r esponse significantly outlasted the dyskinesia effect and progressivel y shortened to parallel the dyskinesia profile at the more advanced cl inical stage. According to kinetic-dynamic modeling, L-DOPA concentrat ions producing 50% of maximum therapeutic and toxic effects (EC50) als o changed independently. EC50 for dyskinesias did not vary significant ly over time. EC50 for the tapping effect was, at the first observatio n, significantly lower than that of the matched value for dyskinesias and progressively rose to values similar to the EC50 for dyskinesias b y the third year of follow-up, These data suggest a dissociation of th e kinetic-dynamic relationship of L-DOPA motor and dyskinesia effects, possibly reflecting different cerebral handling of exogenous levodopa -derived dopamine with disease progression.