title: Levodopa in the treatment of Parkinson's disease: current controversies.
abstract: Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. warren.olanow@mssm.edu
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
authors.forename: Yves
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authors.lastname: Agid
authors.forename: Yoshi
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authors.lastname: Mizuno
authors.forename: Alberto
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authors.lastname: Albanese
authors.forename: Ubaldo
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authors.lastname: Bonuccelli
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authors.lastname: Grandas
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authors.lastname: Hallett
authors.forename: Ole
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authors.lastname: Hornykiewicz
authors.forename: Peter
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authors.lastname: Jenner
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authors.lastname: Katzenschlager
authors.forename: William J
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authors.lastname: Langston
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authors.lastname: LeWitt
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authors.lastname: Melamed
authors.forename: M A
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authors.lastname: Mena
authors.forename: P P
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authors.lastname: Michel
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authors.lastname: Mytilineou
authors.forename: Jose A
authors.initials: JA
authors.lastname: Obeso
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Niall
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authors.lastname: Quinn
authors.forename: R
authors.initials: R
authors.lastname: Raisman-Vozari
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: Christina
authors.initials: C
authors.lastname: Sampaio
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
mesh_terms: D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D011954:Receptors, Dopamine; D007980:Levodopa