Levodopa in the treatment of Parkinson's disease: Current controversies
Identifieur interne : 001732 ( Main/Curation ); précédent : 001731; suivant : 001733Levodopa in the treatment of Parkinson's disease: Current controversies
Auteurs : C. Warren Olanow [États-Unis] ; Yves Agid [France] ; Yoshi Mizuno [Japon] ; Alberto Albanese [Italie] ; U. Bonucelli [Italie] ; Philip Damier [France] ; Justo De Yebenes [Espagne] ; Oscar Gershanik [Argentine] ; Mark Guttman [Canada] ; F. Grandas [Espagne] ; Mark Hallett [États-Unis] ; Ole Hornykiewicz [Autriche] ; Peter Jenner [Royaume-Uni] ; R. Katzenschlager [Royaume-Uni] ; William J. Langston [États-Unis] ; Peter Lewitt [États-Unis] ; Eldad Melamed [Israël] ; M. A. Mena [Espagne] ; P. P. Michel [France] ; Catherine Mytilineou [États-Unis] ; Jose A. Obeso [Espagne] ; Werner Poewe [Autriche] ; Niall Quinn [Royaume-Uni] ; R. Raisman-Vozari [France] ; Ali H. Rajput [Canada] ; Olivier Rascol [France] ; Christina Sampaio [Portugal] ; Fabrizio Stocchi [Italie]Source :
- Movement Disorders [ 0885-3185 ] ; 2004-09.
English descriptors
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. © 2004 Movement Disorder Society
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DOI: 10.1002/mds.20243
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Warren Olanow</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="1"><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hopital de la Salpetriere, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Mizuno, Yoshi" sort="Mizuno, Yoshi" uniqKey="Mizuno Y" first="Yoshi" last="Mizuno">Yoshi Mizuno</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</mods:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><affiliation wicri:level="1"><mods:affiliation>Istituto Nazionale Neurologico, Milano, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Istituto Nazionale Neurologico, Milano</wicri:regionArea></affiliation></author><author><name sortKey="Bonucelli, U" sort="Bonucelli, U" uniqKey="Bonucelli U" first="U." last="Bonucelli">U. 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A." last="Mena">M. A. Mena</name><affiliation wicri:level="1"><mods:affiliation>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Michel, P P" sort="Michel, P P" uniqKey="Michel P" first="P. P." last="Michel">P. P. Michel</name><affiliation wicri:level="1"><mods:affiliation>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Mytilineou, Catherine" sort="Mytilineou, Catherine" uniqKey="Mytilineou C" first="Catherine" last="Mytilineou">Catherine Mytilineou</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="Jose A." last="Obeso">Jose A. Obeso</name><affiliation wicri:level="1"><mods:affiliation>Universitarie of Navarra, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Universitarie of Navarra, Pamplona</wicri:regionArea></affiliation></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation wicri:level="1"><mods:affiliation>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</mods:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol</wicri:regionArea></affiliation></author><author><name sortKey="Quinn, Niall" sort="Quinn, Niall" uniqKey="Quinn N" first="Niall" last="Quinn">Niall Quinn</name><affiliation wicri:level="1"><mods:affiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</mods:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Neurology, Department of Clinical Neurology, Queen Square, London</wicri:regionArea></affiliation></author><author><name sortKey="Raisman Ozari, R" sort="Raisman Ozari, R" uniqKey="Raisman Ozari R" first="R." last="Raisman-Vozari">R. Raisman-Vozari</name><affiliation wicri:level="1"><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hopital de la Salpetriere, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><mods:affiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Royal University Hospital, Saskatoon, Saskatchewan</wicri:regionArea></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><mods:affiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Sampaio, Christina" sort="Sampaio, Christina" uniqKey="Sampaio C" first="Christina" last="Sampaio">Christina Sampaio</name><affiliation wicri:level="1"><mods:affiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</mods:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>R Dr Antonio Loureiro Borges, Lisbon</wicri:regionArea></affiliation></author><author><name sortKey="Stocchi, Fabrizio" sort="Stocchi, Fabrizio" uniqKey="Stocchi F" first="Fabrizio" last="Stocchi">Fabrizio Stocchi</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:BB30349AF852C8DA89AA6C25FC669A192C301574</idno><date when="2004" year="2004">2004</date><idno type="doi">10.1002/mds.20243</idno><idno type="url">https://api.istex.fr/document/BB30349AF852C8DA89AA6C25FC669A192C301574/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001983</idno><idno type="wicri:Area/Main/Curation">001732</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Levodopa in the treatment of Parkinson's disease: Current controversies</title><author><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C. Warren" last="Olanow">C. Warren Olanow</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="1"><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hopital de la Salpetriere, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Mizuno, Yoshi" sort="Mizuno, Yoshi" uniqKey="Mizuno Y" first="Yoshi" last="Mizuno">Yoshi Mizuno</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</mods:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo</wicri:regionArea></affiliation></author><author><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><affiliation wicri:level="1"><mods:affiliation>Istituto Nazionale Neurologico, Milano, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Istituto Nazionale Neurologico, Milano</wicri:regionArea></affiliation></author><author><name sortKey="Bonucelli, U" sort="Bonucelli, U" uniqKey="Bonucelli U" first="U." last="Bonucelli">U. Bonucelli</name><affiliation wicri:level="1"><mods:affiliation>Department of Neuroscience, University of Pisa, Capezzano‐Pianore, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neuroscience, University of Pisa, Capezzano‐Pianore</wicri:regionArea></affiliation></author><author><name sortKey="Damier, Philip" sort="Damier, Philip" uniqKey="Damier P" first="Philip" last="Damier">Philip Damier</name><affiliation wicri:level="1"><mods:affiliation>Hopital Laennec, Clinique Neurologique, Nantes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hopital Laennec, Clinique Neurologique, Nantes</wicri:regionArea></affiliation></author><author><name sortKey="De Yebenes, Justo" sort="De Yebenes, Justo" uniqKey="De Yebenes J" first="Justo" last="De Yebenes">Justo De Yebenes</name><affiliation wicri:level="1"><mods:affiliation>Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Gershanik, Oscar" sort="Gershanik, Oscar" uniqKey="Gershanik O" first="Oscar" last="Gershanik">Oscar Gershanik</name><affiliation wicri:level="1"><mods:affiliation>Hopital Frances, Centro Neurold”gico, La Rioja, Buenos Aires, Argentina</mods:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Hopital Frances, Centro Neurold”gico, La Rioja, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Guttman, Mark" sort="Guttman, Mark" uniqKey="Guttman M" first="Mark" last="Guttman">Mark Guttman</name><affiliation wicri:level="1"><mods:affiliation>University of Toronto, Markham, Ontario, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>University of Toronto, Markham, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Grandas, F" sort="Grandas, F" uniqKey="Grandas F" first="F." last="Grandas">F. Grandas</name><affiliation wicri:level="1"><mods:affiliation>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Hallett, Mark" sort="Hallett, Mark" uniqKey="Hallett M" first="Mark" last="Hallett">Mark Hallett</name><affiliation wicri:level="1"><mods:affiliation>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Hornykiewicz, Ole" sort="Hornykiewicz, Ole" uniqKey="Hornykiewicz O" first="Ole" last="Hornykiewicz">Ole Hornykiewicz</name><affiliation wicri:level="1"><mods:affiliation>Brain Research Institute, Vienna University Medical School, Vienna, Austria</mods:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Brain Research Institute, Vienna University Medical School, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name><affiliation wicri:level="1"><mods:affiliation>King's College London, Hodgkin Building, Guy's Campus, London, United Kingdom</mods:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>King's College London, Hodgkin Building, Guy's Campus, London</wicri:regionArea></affiliation></author><author><name sortKey="Katzenschlager, R" sort="Katzenschlager, R" uniqKey="Katzenschlager R" first="R." last="Katzenschlager">R. Katzenschlager</name><affiliation wicri:level="1"><mods:affiliation>National Hospital for Neurology and Neurosurgery, London, United Kingdom</mods:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Hospital for Neurology and Neurosurgery, London</wicri:regionArea></affiliation></author><author><name sortKey="Langston, William J" sort="Langston, William J" uniqKey="Langston W" first="William J." last="Langston">William J. Langston</name><affiliation wicri:level="1"><mods:affiliation>The Parkinson's Institute, Sunnyvale, California, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Parkinson's Institute, Sunnyvale, California</wicri:regionArea></affiliation></author><author><name sortKey="Lewitt, Peter" sort="Lewitt, Peter" uniqKey="Lewitt P" first="Peter" last="Lewitt">Peter Lewitt</name><affiliation wicri:level="1"><mods:affiliation>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan</wicri:regionArea></affiliation></author><author><name sortKey="Melamed, Eldad" sort="Melamed, Eldad" uniqKey="Melamed E" first="Eldad" last="Melamed">Eldad Melamed</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel</mods:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva</wicri:regionArea></affiliation></author><author><name sortKey="Mena, M A" sort="Mena, M A" uniqKey="Mena M" first="M. A." last="Mena">M. A. Mena</name><affiliation wicri:level="1"><mods:affiliation>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Michel, P P" sort="Michel, P P" uniqKey="Michel P" first="P. P." last="Michel">P. P. Michel</name><affiliation wicri:level="1"><mods:affiliation>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Mytilineou, Catherine" sort="Mytilineou, Catherine" uniqKey="Mytilineou C" first="Catherine" last="Mytilineou">Catherine Mytilineou</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="Jose A." last="Obeso">Jose A. Obeso</name><affiliation wicri:level="1"><mods:affiliation>Universitarie of Navarra, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Universitarie of Navarra, Pamplona</wicri:regionArea></affiliation></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation wicri:level="1"><mods:affiliation>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</mods:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol</wicri:regionArea></affiliation></author><author><name sortKey="Quinn, Niall" sort="Quinn, Niall" uniqKey="Quinn N" first="Niall" last="Quinn">Niall Quinn</name><affiliation wicri:level="1"><mods:affiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</mods:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Neurology, Department of Clinical Neurology, Queen Square, London</wicri:regionArea></affiliation></author><author><name sortKey="Raisman Ozari, R" sort="Raisman Ozari, R" uniqKey="Raisman Ozari R" first="R." last="Raisman-Vozari">R. Raisman-Vozari</name><affiliation wicri:level="1"><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hopital de la Salpetriere, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><mods:affiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Royal University Hospital, Saskatoon, Saskatchewan</wicri:regionArea></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><mods:affiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Sampaio, Christina" sort="Sampaio, Christina" uniqKey="Sampaio C" first="Christina" last="Sampaio">Christina Sampaio</name><affiliation wicri:level="1"><mods:affiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</mods:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>R Dr Antonio Loureiro Borges, Lisbon</wicri:regionArea></affiliation></author><author><name sortKey="Stocchi, Fabrizio" sort="Stocchi, Fabrizio" uniqKey="Stocchi F" first="Fabrizio" last="Stocchi">Fabrizio Stocchi</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2004-09">2004-09</date><biblScope unit="volume">19</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="997">997</biblScope><biblScope unit="page" to="1005">1005</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">BB30349AF852C8DA89AA6C25FC669A192C301574</idno><idno type="DOI">10.1002/mds.20243</idno><idno type="ArticleID">MDS20243</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>dyskinesia</term><term>levodopa</term><term>motor complications</term><term>neurotoxicity</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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. © 2004 Movement Disorder Society</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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