SUPPRESSION OF DYSKINESIAS IN ADVANCED PARKINSONS-DISEASE .1. CONTINUOUS INTRAVENOUS LEVODOPA SHIFTS DOSE-RESPONSE FOR PRODUCTION OF DYSKINESIAS BUT NOT FOR RELIEF OF PARKINSONISM IN PATIENTS WITH ADVANCED PARKINSONS-DISEASE

We characterized the clinical dose-response curves for relief of parki nsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's d isease (PD) and fluctuating responses to oral levodopa/carbidopa. Dose response to ramped intravenous levodopa infusion was measured after o vernight drug withdrawal on two occasions: first after chronic, interm ittent oral levodopa/carbidopa, and second after 3 to 5 days of contin uous intravenous levodopa. Continuous intravenous levodopa shifted the dyskinesia dose-response curve to the right, reduced maximum dyskines ia activity, but did not significantly alter dose response for relief of parkinsonism. Improvement in dyskinesia was apparent by the second day of continuous levodopa, during which ratios of plasma dopa/3-O-met hyldopa remained constant. Our results support the hypothesis that rel ief of parkinsonism and production of dyskinesia by levodopa occur by separate mechanisms.