Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease.
We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa. Dose response to ramped intravenous levodopa infusion was measured after overnight drug withdrawal on two occasions: first after chronic, intermittent oral levodopa/carbidopa, and second after 3 to 5 days of continuous intravenous levodopa. Continuous intravenous levodopa shifted the dyskinesia dose-response curve to the right, reduced maximum dyskinesia 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-methyldopa remained constant. Our results support the hypothesis that relief of parkinsonism and production of dyskinesia by levodopa occur by separate mechanisms.
Schuh
L A
LA
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
Bennett
J P
JP
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects; D004295:Dihydroxyphenylalanine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000209:etiology*; D010300:Parkinson Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
D000978:Antiparkinson Agents; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D014443:Tyrosine; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D002230:Carbidopa; C008404:3-methoxytyrosine