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Levodopa in the treatment of Parkinson's disease: current controversies.
Mov Disord. 2004 Sep; 19(9):997-1005.MD

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+Show Affiliations

Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. warren.olanow@mssm.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

15372588

Citation

Olanow, C Warren, et al. "Levodopa in the Treatment of Parkinson's Disease: Current Controversies." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 19, no. 9, 2004, pp. 997-1005.
Olanow CW, Agid Y, Mizuno Y, et al. Levodopa in the treatment of Parkinson's disease: current controversies. Mov Disord. 2004;19(9):997-1005.
Olanow, C. W., Agid, Y., Mizuno, Y., Albanese, A., Bonuccelli, U., Bonucelli, U., Damier, P., De Yebenes, J., Gershanik, O., Guttman, M., Grandas, F., Hallett, M., Hornykiewicz, O., Jenner, P., Katzenschlager, R., Langston, W. J., LeWitt, P., Melamed, E., Mena, M. A., ... Stocchi, F. (2004). Levodopa in the treatment of Parkinson's disease: current controversies. Movement Disorders : Official Journal of the Movement Disorder Society, 19(9), 997-1005.
Olanow CW, et al. Levodopa in the Treatment of Parkinson's Disease: Current Controversies. Mov Disord. 2004;19(9):997-1005. PubMed PMID: 15372588.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Levodopa in the treatment of Parkinson's disease: current controversies. AU - Olanow,C Warren, AU - Agid,Yves, AU - Mizuno,Yoshi, AU - Albanese,Alberto, AU - Bonuccelli,Ubaldo, AU - Bonucelli,U, AU - Damier,Philip, AU - De Yebenes,Justo, AU - Gershanik,Oscar, AU - Guttman,Mark, AU - Grandas,F, AU - Hallett,Mark, AU - Hornykiewicz,Ole, AU - Jenner,Peter, AU - Katzenschlager,R, AU - Langston,William J, AU - LeWitt,Peter, AU - Melamed,Eldad, AU - Mena,M A, AU - Michel,P P, AU - Mytilineou,Catherine, AU - Obeso,Jose A, AU - Poewe,Werner, AU - Quinn,Niall, AU - Raisman-Vozari,R, AU - Rajput,Ali H, AU - Rascol,Olivier, AU - Sampaio,Christina, AU - Stocchi,Fabrizio, PY - 2004/9/17/pubmed PY - 2004/12/22/medline PY - 2004/9/17/entrez SP - 997 EP - 1005 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 19 IS - 9 N2 - 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. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/15372588/Levodopa_in_the_treatment_of_Parkinson's_disease:_current_controversies_ L2 - https://doi.org/10.1002/mds.20243 DB - PRIME DP - Unbound Medicine ER -