Levodopa in the treatment of Parkinson's disease: Current controversies

被引：282

作者：

Olanow, CW ^{[1
]}

Agid, Y

Mizuno, Y

Albanese, A

Bonucelli, U

Damier, P

De Yebenes, J

Gershanik, O

Guttman, M

Grandas, F

Hallett, M

Hornykiewicz, O

Jenner, P

Katzenschlager, R

Langston, WJ

LeWitt, P

Melamed, E

Mena, MA

Michel, PP

Mytilineou, C

Obeso, JA

Poewe, W

Quinn, N

Rajput, AH

Rascol, O

Sampaio, C

Stocchi, F

机构：

[1] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA

[2] Hop La Pitie Salpetriere, Paris, France

[3] Jutendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, Tokyo, Japan

[4] Ist Nazl Neurol, Milan, Italy

[5] Univ Pisa, Dept Neurosci, I-56100 Pisa, Italy

[6] Hop Laennec, Neurol Clin, Nantes, France

[7] Univ Autonoma Madrid, Fdn Jimenez Diaz, Madrid, Spain

[8] Hop Frances, Ctr Neuroldgico, Buenos Aires, DF, Argentina

[9] Univ Toronto, Markham, ON, Canada

[10] Hop Gen G Maranon, Madrid, Spain

[11] Natl Inst Neurol Dis Ctr, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA

[12] Univ Vienna, Sch Med, Brain Res Inst, Vienna, Austria

[13] Kings Coll London, London WC2R 2LS, England

[14] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England

[15] Parkinsons Inst, Sunnyvale, CA USA

[16] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA

[17] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA

[18] Rabin Med Ctr, Dept Neurol, Petah Tiqwa, Israel

[19] Hosp Ramon & Cajal, Dept Neurobiol Invest, Ctr Colmenar, E-28034 Madrid, Spain

[20] Hop La Pitie Salpetriere, INSERM, Paris, France

[21] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA

[22] Univ Navarra, E-31080 Pamplona, Spain

[23] Univ Innsbruck Hosp, Dept Neurol, A-6020 Innsbruck, Tyrol, Austria

[24] Neurol Inst, Dept Clin Neurol, London, England

[25] Hop La Pitie Salpetriere, Paris, France

[26] Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada

[27] Clin Univ Ctr, Fac Med, Toulouse, France

[28] R Dr Antonio Loureiro Borges, Lisbon, Portugal

[29] Univ Roma La Sapienza, Hosp San Raffaele, Dept Neurosci, Rome, Italy

来源：

MOVEMENT DISORDERS | 2004年 / 19卷 / 09期

关键词：

Parkinson's disease; levodopa; neurotoxicity; dyskinesia; motor complications;

D O I：

10.1002/mds.20243

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 rnotor 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. (C) 2004 Movement Disorder Society.

引用

页码：997 / 1005

页数：9

共 132 条

[31]

DEXTER DT, 1987, LANCET, V2, P1219

[32] INCREASED LEVELS OF LIPID HYDROPEROXIDES IN THE PARKINSONIAN SUBSTANTIA-NIGRA - AN HPLC AND ESR STUDY [J].