title: Effects of supra-threshold levodopa doses on dyskinesias in advanced Parkinson's disease.
abstract: The levodopa (LD) dose-antiparkinsonian response relationship becomes progressively steeper with advancing Parkinson's disease (PD). To establish the dose-response profile for the dyskinesiogenic effect of LD, we administered intravenous LD over a wide dose range to 25 patients with advanced PD. As expected in these patients with nonexistent therapeutic windows, the threshold doses (TD) for both motor effects were similar. Just around the TD, the relationship between LD dose and the magnitude of antiparkinsonian and dyskinesiogenic responses inclined steeply, reaching a plateau above 1.5 x TD. Response duration, however, continued to increase. The findings suggest that attempts to ameliorate dyskinesias in advanced PD patients by giving smaller, more frequent LD doses may be counter-productive due to shorter motor responses, more "off" time, and dose failures, while some may, in fact, benefit from higher LD doses to assure a full response and prolong its duration.
authors.affiliation: Experimental Therapoutics Branch, National Institutes of Health, Bethesda, MD 20892-1406, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Metman
authors.forename: P
authors.initials: P
authors.lastname: van den Munckhof
authors.forename: A A
authors.initials: AA
authors.lastname: Klaassen
authors.forename: P
authors.initials: P
authors.lastname: Blanchet
authors.forename: M M
authors.initials: MM
authors.lastname: Mouradian
authors.forename: T N
authors.initials: TN
authors.lastname: Chase
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000175:diagnosis / Q000188:drug therapy*; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy*; D010919:Placebos; D012720:Severity of Illness Index
chemical_list: D000978:Antiparkinson Agents; D010919:Placebos; D007980:Levodopa