Levodopa in the treatment of Parkinson's disease: Current controversies
Identifieur interne : 001841 ( Istex/Corpus ); précédent : 001840; suivant : 001842Levodopa in the treatment of Parkinson's disease: Current controversies
Auteurs : C. Warren Olanow ; Yves Agid ; Yoshi Mizuno ; Alberto Albanese ; U. Bonucelli ; Philip Damier ; Justo De Yebenes ; Oscar Gershanik ; Mark Guttman ; F. Grandas ; Mark Hallett ; Ole Hornykiewicz ; Peter Jenner ; R. Katzenschlager ; William J. Langston ; Peter Lewitt ; Eldad Melamed ; M. A. Mena ; P. P. Michel ; Catherine Mytilineou ; Jose A. Obeso ; Werner Poewe ; Niall Quinn ; R. Raisman-Vozari ; Ali H. Rajput ; Olivier Rascol ; Christina Sampaio ; Fabrizio StocchiSource :
- 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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ISTEX:BB30349AF852C8DA89AA6C25FC669A192C301574Le document en format XML
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Warren Olanow</name><affiliation><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029</mods:affiliation></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mizuno, Yoshi" sort="Mizuno, Yoshi" uniqKey="Mizuno Y" first="Yoshi" last="Mizuno">Yoshi Mizuno</name><affiliation><mods:affiliation>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><affiliation><mods:affiliation>Istituto Nazionale Neurologico, Milano, Italy</mods:affiliation></affiliation></author><author><name sortKey="Bonucelli, U" sort="Bonucelli, U" uniqKey="Bonucelli U" first="U." last="Bonucelli">U. 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Grandas</name><affiliation><mods:affiliation>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid, Spain</mods:affiliation></affiliation></author><author><name sortKey="Hallett, Mark" sort="Hallett, Mark" uniqKey="Hallett M" first="Mark" last="Hallett">Mark Hallett</name><affiliation><mods:affiliation>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland, USA</mods:affiliation></affiliation></author><author><name sortKey="Hornykiewicz, Ole" sort="Hornykiewicz, Ole" uniqKey="Hornykiewicz O" first="Ole" last="Hornykiewicz">Ole Hornykiewicz</name><affiliation><mods:affiliation>Brain Research Institute, Vienna University Medical School, Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name><affiliation><mods:affiliation>King's College London, Hodgkin Building, Guy's Campus, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Katzenschlager, R" sort="Katzenschlager, R" uniqKey="Katzenschlager R" first="R." last="Katzenschlager">R. Katzenschlager</name><affiliation><mods:affiliation>National Hospital for Neurology and Neurosurgery, London, United Kingdom</mods:affiliation></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><mods:affiliation>The Parkinson's Institute, Sunnyvale, California, USA</mods:affiliation></affiliation></author><author><name sortKey="Lewitt, Peter" sort="Lewitt, Peter" uniqKey="Lewitt P" first="Peter" last="Lewitt">Peter Lewitt</name><affiliation><mods:affiliation>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan, USA</mods:affiliation></affiliation></author><author><name sortKey="Melamed, Eldad" sort="Melamed, Eldad" uniqKey="Melamed E" first="Eldad" last="Melamed">Eldad Melamed</name><affiliation><mods:affiliation>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel</mods:affiliation></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><mods:affiliation>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</mods:affiliation></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><mods:affiliation>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mytilineou, Catherine" sort="Mytilineou, Catherine" uniqKey="Mytilineou C" first="Catherine" last="Mytilineou">Catherine Mytilineou</name><affiliation><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation></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><mods:affiliation>Universitarie of Navarra, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation><mods:affiliation>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</mods:affiliation></affiliation></author><author><name sortKey="Quinn, Niall" sort="Quinn, Niall" uniqKey="Quinn N" first="Niall" last="Quinn">Niall Quinn</name><affiliation><mods:affiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</mods:affiliation></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><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation></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><mods:affiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</mods:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><mods:affiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Sampaio, Christina" sort="Sampaio, Christina" uniqKey="Sampaio C" first="Christina" last="Sampaio">Christina Sampaio</name><affiliation><mods:affiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Stocchi, Fabrizio" sort="Stocchi, Fabrizio" uniqKey="Stocchi F" first="Fabrizio" last="Stocchi">Fabrizio Stocchi</name><affiliation><mods:affiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</mods:affiliation></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/Istex/Corpus">001841</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001841</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><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029</mods:affiliation></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mizuno, Yoshi" sort="Mizuno, Yoshi" uniqKey="Mizuno Y" first="Yoshi" last="Mizuno">Yoshi Mizuno</name><affiliation><mods:affiliation>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><affiliation><mods:affiliation>Istituto Nazionale Neurologico, Milano, Italy</mods:affiliation></affiliation></author><author><name sortKey="Bonucelli, U" sort="Bonucelli, U" uniqKey="Bonucelli U" first="U." last="Bonucelli">U. Bonucelli</name><affiliation><mods:affiliation>Department of Neuroscience, University of Pisa, Capezzano‐Pianore, Italy</mods:affiliation></affiliation></author><author><name sortKey="Damier, Philip" sort="Damier, Philip" uniqKey="Damier P" first="Philip" last="Damier">Philip Damier</name><affiliation><mods:affiliation>Hopital Laennec, Clinique Neurologique, Nantes, France</mods:affiliation></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><mods:affiliation>Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain</mods:affiliation></affiliation></author><author><name sortKey="Gershanik, Oscar" sort="Gershanik, Oscar" uniqKey="Gershanik O" first="Oscar" last="Gershanik">Oscar Gershanik</name><affiliation><mods:affiliation>Hopital Frances, Centro Neurold”gico, La Rioja, Buenos Aires, Argentina</mods:affiliation></affiliation></author><author><name sortKey="Guttman, Mark" sort="Guttman, Mark" uniqKey="Guttman M" first="Mark" last="Guttman">Mark Guttman</name><affiliation><mods:affiliation>University of Toronto, Markham, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Grandas, F" sort="Grandas, F" uniqKey="Grandas F" first="F." last="Grandas">F. Grandas</name><affiliation><mods:affiliation>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid, Spain</mods:affiliation></affiliation></author><author><name sortKey="Hallett, Mark" sort="Hallett, Mark" uniqKey="Hallett M" first="Mark" last="Hallett">Mark Hallett</name><affiliation><mods:affiliation>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland, USA</mods:affiliation></affiliation></author><author><name sortKey="Hornykiewicz, Ole" sort="Hornykiewicz, Ole" uniqKey="Hornykiewicz O" first="Ole" last="Hornykiewicz">Ole Hornykiewicz</name><affiliation><mods:affiliation>Brain Research Institute, Vienna University Medical School, Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name><affiliation><mods:affiliation>King's College London, Hodgkin Building, Guy's Campus, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Katzenschlager, R" sort="Katzenschlager, R" uniqKey="Katzenschlager R" first="R." last="Katzenschlager">R. Katzenschlager</name><affiliation><mods:affiliation>National Hospital for Neurology and Neurosurgery, London, United Kingdom</mods:affiliation></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><mods:affiliation>The Parkinson's Institute, Sunnyvale, California, USA</mods:affiliation></affiliation></author><author><name sortKey="Lewitt, Peter" sort="Lewitt, Peter" uniqKey="Lewitt P" first="Peter" last="Lewitt">Peter Lewitt</name><affiliation><mods:affiliation>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan, USA</mods:affiliation></affiliation></author><author><name sortKey="Melamed, Eldad" sort="Melamed, Eldad" uniqKey="Melamed E" first="Eldad" last="Melamed">Eldad Melamed</name><affiliation><mods:affiliation>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel</mods:affiliation></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><mods:affiliation>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</mods:affiliation></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><mods:affiliation>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mytilineou, Catherine" sort="Mytilineou, Catherine" uniqKey="Mytilineou C" first="Catherine" last="Mytilineou">Catherine Mytilineou</name><affiliation><mods:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</mods:affiliation></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><mods:affiliation>Universitarie of Navarra, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation><mods:affiliation>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</mods:affiliation></affiliation></author><author><name sortKey="Quinn, Niall" sort="Quinn, Niall" uniqKey="Quinn N" first="Niall" last="Quinn">Niall Quinn</name><affiliation><mods:affiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</mods:affiliation></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><mods:affiliation>Hopital de la Salpetriere, Paris, France</mods:affiliation></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><mods:affiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</mods:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><mods:affiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</mods:affiliation></affiliation></author><author><name sortKey="Sampaio, Christina" sort="Sampaio, Christina" uniqKey="Sampaio C" first="Christina" last="Sampaio">Christina Sampaio</name><affiliation><mods:affiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Stocchi, Fabrizio" sort="Stocchi, Fabrizio" uniqKey="Stocchi F" first="Fabrizio" last="Stocchi">Fabrizio Stocchi</name><affiliation><mods:affiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</mods:affiliation></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><istex><corpusName>wiley</corpusName><author><json:item><name>C. Warren Olanow</name><affiliations><json:string>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</json:string><json:string>Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029</json:string></affiliations></json:item><json:item><name>Yves Agid</name><affiliations><json:string>Hopital de la Salpetriere, Paris, France</json:string></affiliations></json:item><json:item><name>Yoshi Mizuno</name><affiliations><json:string>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Alberto Albanese</name><affiliations><json:string>Istituto Nazionale Neurologico, Milano, Italy</json:string></affiliations></json:item><json:item><name>U. Bonucelli</name><affiliations><json:string>Department of Neuroscience, University of Pisa, Capezzano‐Pianore, Italy</json:string></affiliations></json:item><json:item><name>Philip Damier</name><affiliations><json:string>Hopital Laennec, Clinique Neurologique, Nantes, France</json:string></affiliations></json:item><json:item><name>Justo De Yebenes</name><affiliations><json:string>Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain</json:string></affiliations></json:item><json:item><name>Oscar Gershanik</name><affiliations><json:string>Hopital Frances, Centro Neurold”gico, La Rioja, Buenos Aires, Argentina</json:string></affiliations></json:item><json:item><name>Mark Guttman</name><affiliations><json:string>University of Toronto, Markham, Ontario, Canada</json:string></affiliations></json:item><json:item><name>F. Grandas</name><affiliations><json:string>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid, Spain</json:string></affiliations></json:item><json:item><name>Mark Hallett</name><affiliations><json:string>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland, USA</json:string></affiliations></json:item><json:item><name>Ole Hornykiewicz</name><affiliations><json:string>Brain Research Institute, Vienna University Medical School, Vienna, Austria</json:string></affiliations></json:item><json:item><name>Peter Jenner</name><affiliations><json:string>King's College London, Hodgkin Building, Guy's Campus, London, United Kingdom</json:string></affiliations></json:item><json:item><name>R. Katzenschlager</name><affiliations><json:string>National Hospital for Neurology and Neurosurgery, London, United Kingdom</json:string></affiliations></json:item><json:item><name>William J. Langston</name><affiliations><json:string>The Parkinson's Institute, Sunnyvale, California, USA</json:string></affiliations></json:item><json:item><name>Peter LeWitt</name><affiliations><json:string>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan, USA</json:string></affiliations></json:item><json:item><name>Eldad Melamed</name><affiliations><json:string>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel</json:string></affiliations></json:item><json:item><name>M.A. Mena</name><affiliations><json:string>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</json:string></affiliations></json:item><json:item><name>P.P. Michel</name><affiliations><json:string>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</json:string></affiliations></json:item><json:item><name>Catherine Mytilineou</name><affiliations><json:string>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</json:string></affiliations></json:item><json:item><name>Jose A. Obeso</name><affiliations><json:string>Universitarie of Navarra, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>Werner Poewe</name><affiliations><json:string>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</json:string></affiliations></json:item><json:item><name>Niall Quinn</name><affiliations><json:string>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</json:string></affiliations></json:item><json:item><name>R. Raisman‐Vozari</name><affiliations><json:string>Hopital de la Salpetriere, Paris, France</json:string></affiliations></json:item><json:item><name>Ali H. Rajput</name><affiliations><json:string>Royal University Hospital, Saskatoon, Saskatchewan, Canada</json:string></affiliations></json:item><json:item><name>Olivier Rascol</name><affiliations><json:string>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</json:string></affiliations></json:item><json:item><name>Christina Sampaio</name><affiliations><json:string>R Dr Antonio Loureiro Borges, Lisbon, Portugal</json:string></affiliations></json:item><json:item><name>Fabrizio Stocchi</name><affiliations><json:string>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>levodopa</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neurotoxicity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dyskinesia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>motor complications</value></json:item></subject><articleId><json:string>MDS20243</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>reviewArticle</json:string></originalGenre><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. 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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. 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exposure</title></json:item></refBibs><genre><json:string>review-article</json:string></genre><host><volume>19</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>9</total><last>1005</last><first>997</first></pages><issn><json:string>0885-3185</json:string></issn><issue>9</issue><subject><json:item><value>Research Review</value></json:item></subject><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>clinical neurology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix></categories><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><doi><json:string>10.1002/mds.20243</json:string></doi><id>BB30349AF852C8DA89AA6C25FC669A192C301574</id><score>0.13457373</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/BB30349AF852C8DA89AA6C25FC669A192C301574/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/BB30349AF852C8DA89AA6C25FC669A192C301574/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/BB30349AF852C8DA89AA6C25FC669A192C301574/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Levodopa in the treatment of Parkinson's disease: Current controversies</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Copyright © 2004 Movement Disorder Society</p></availability><date>2004</date></publicationStmt><notesStmt><note>Novartis Pharma AG</note><note>Orion Corporation Orion Pharma</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Levodopa in the treatment of Parkinson's disease: Current controversies</title><author xml:id="author-1"><persName><forename type="first">C. Warren</forename><surname>Olanow</surname></persName><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029</affiliation></author><author xml:id="author-2"><persName><forename type="first">Yves</forename><surname>Agid</surname></persName><affiliation>Hopital de la Salpetriere, Paris, France</affiliation></author><author xml:id="author-3"><persName><forename type="first">Yoshi</forename><surname>Mizuno</surname></persName><affiliation>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</affiliation></author><author xml:id="author-4"><persName><forename type="first">Alberto</forename><surname>Albanese</surname></persName><affiliation>Istituto Nazionale Neurologico, Milano, Italy</affiliation></author><author xml:id="author-5"><persName><forename type="first">U.</forename><surname>Bonucelli</surname></persName><affiliation>Department of Neuroscience, University of Pisa, Capezzano‐Pianore, Italy</affiliation></author><author xml:id="author-6"><persName><forename type="first">Philip</forename><surname>Damier</surname></persName><affiliation>Hopital Laennec, Clinique Neurologique, Nantes, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Justo</forename><surname>De Yebenes</surname></persName><affiliation>Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain</affiliation></author><author xml:id="author-8"><persName><forename type="first">Oscar</forename><surname>Gershanik</surname></persName><affiliation>Hopital Frances, Centro Neurold”gico, La Rioja, Buenos Aires, Argentina</affiliation></author><author xml:id="author-9"><persName><forename type="first">Mark</forename><surname>Guttman</surname></persName><affiliation>University of Toronto, Markham, Ontario, Canada</affiliation></author><author xml:id="author-10"><persName><forename type="first">F.</forename><surname>Grandas</surname></persName><affiliation>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid, Spain</affiliation></author><author xml:id="author-11"><persName><forename type="first">Mark</forename><surname>Hallett</surname></persName><affiliation>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland, USA</affiliation></author><author xml:id="author-12"><persName><forename type="first">Ole</forename><surname>Hornykiewicz</surname></persName><affiliation>Brain Research Institute, Vienna University Medical School, Vienna, Austria</affiliation></author><author xml:id="author-13"><persName><forename type="first">Peter</forename><surname>Jenner</surname></persName><affiliation>King's College London, Hodgkin Building, Guy's Campus, London, United Kingdom</affiliation></author><author xml:id="author-14"><persName><forename type="first">R.</forename><surname>Katzenschlager</surname></persName><affiliation>National Hospital for Neurology and Neurosurgery, London, United Kingdom</affiliation></author><author xml:id="author-15"><persName><forename type="first">William J.</forename><surname>Langston</surname></persName><affiliation>The Parkinson's Institute, Sunnyvale, California, USA</affiliation></author><author xml:id="author-16"><persName><forename type="first">Peter</forename><surname>LeWitt</surname></persName><affiliation>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan, USA</affiliation></author><author xml:id="author-17"><persName><forename type="first">Eldad</forename><surname>Melamed</surname></persName><affiliation>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel</affiliation></author><author xml:id="author-18"><persName><forename type="first">M.A.</forename><surname>Mena</surname></persName><affiliation>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</affiliation></author><author xml:id="author-19"><persName><forename type="first">P.P.</forename><surname>Michel</surname></persName><affiliation>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</affiliation></author><author xml:id="author-20"><persName><forename type="first">Catherine</forename><surname>Mytilineou</surname></persName><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation></author><author xml:id="author-21"><persName><forename type="first">Jose A.</forename><surname>Obeso</surname></persName><affiliation>Universitarie of Navarra, Pamplona, Spain</affiliation></author><author xml:id="author-22"><persName><forename type="first">Werner</forename><surname>Poewe</surname></persName><affiliation>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</affiliation></author><author xml:id="author-23"><persName><forename type="first">Niall</forename><surname>Quinn</surname></persName><affiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</affiliation></author><author xml:id="author-24"><persName><forename type="first">R.</forename><surname>Raisman‐Vozari</surname></persName><affiliation>Hopital de la Salpetriere, Paris, France</affiliation></author><author xml:id="author-25"><persName><forename type="first">Ali H.</forename><surname>Rajput</surname></persName><affiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</affiliation></author><author xml:id="author-26"><persName><forename type="first">Olivier</forename><surname>Rascol</surname></persName><affiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</affiliation></author><author xml:id="author-27"><persName><forename type="first">Christina</forename><surname>Sampaio</surname></persName><affiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</affiliation></author><author xml:id="author-28"><persName><forename type="first">Fabrizio</forename><surname>Stocchi</surname></persName><affiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="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></monogr><idno type="istex">BB30349AF852C8DA89AA6C25FC669A192C301574</idno><idno type="DOI">10.1002/mds.20243</idno><idno type="ArticleID">MDS20243</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>Parkinson's disease</term></item><item><term>levodopa</term></item><item><term>neurotoxicity</term></item><item><term>dyskinesia</term></item><item><term>motor complications</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Review</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2003-08-20">Received</change><change when="2004-05-05">Registration</change><change when="2004-09">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/BB30349AF852C8DA89AA6C25FC669A192C301574/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="90"><doi origin="wiley" registered="yes">10.1002/mds.v19:9</doi><numberingGroup><numbering type="journalVolume" number="19">19</numbering><numbering type="journalIssue">9</numbering></numberingGroup><coverDate startDate="2004-09">September 2004</coverDate></publicationMeta><publicationMeta level="unit" type="reviewArticle" position="10" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.20243</doi><idGroup><id type="unit" value="MDS20243"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Research Review</title><title type="tocHeading1">Research Reviews</title></titleGroup><copyright ownership="thirdParty">Copyright © 2004 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2003-08-20"></event><event type="manuscriptRevised" date="2004-05-03"></event><event type="manuscriptAccepted" date="2004-05-05"></event><event type="firstOnline" date="2004-07-30"></event><event type="publishedOnlineFinalForm" date="2004-08-30"></event><event type="publishedOnlineAcceptedOrEarlyUnpaginated" date="2004-07-30"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.27 mode:FullText source:FullText result:FullText" date="2010-11-22"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">997</numbering><numbering type="pageLast">1005</numbering></numberingGroup><correspondenceTo>Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS20243.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="131"></count><count type="wordTotal" number="7472"></count></countGroup><titleGroup><title type="main" xml:lang="en">Levodopa in the treatment of Parkinson's disease: Current controversies</title><title type="short" xml:lang="en">Levodopa: Current Controversies</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>C. Warren</givenNames><familyName>Olanow</familyName></personName><contactDetails><email>warren.olanow@mssm.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Yves</givenNames><familyName>Agid</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Yoshi</givenNames><familyName>Mizuno</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Alberto</givenNames><familyName>Albanese</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af5"><personName><givenNames>U.</givenNames><familyName>Bonucelli</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Philip</givenNames><familyName>Damier</familyName></personName></creator><creator xml:id="au7" creatorRole="author" 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of Neurology, Innsbruck, Tyrol, Austria</unparsedAffiliation></affiliation><affiliation xml:id="af23" countryCode="GB" type="organization"><unparsedAffiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af24" countryCode="FR" type="organization"><unparsedAffiliation>Hopital de la Salpetriere, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af25" countryCode="CA" type="organization"><unparsedAffiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af26" countryCode="FR" type="organization"><unparsedAffiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</unparsedAffiliation></affiliation><affiliation xml:id="af27" countryCode="PT" type="organization"><unparsedAffiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</unparsedAffiliation></affiliation><affiliation xml:id="af28" countryCode="IT" type="organization"><unparsedAffiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">levodopa</keyword><keyword xml:id="kwd3">neurotoxicity</keyword><keyword xml:id="kwd4">dyskinesia</keyword><keyword xml:id="kwd5">motor complications</keyword></keywordGroup><fundingInfo><fundingAgency>Novartis Pharma AG</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Orion Corporation Orion Pharma</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>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</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Levodopa in the treatment of Parkinson's disease: Current controversies</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Levodopa: Current Controversies</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Levodopa in the treatment of Parkinson's disease: Current controversies</title></titleInfo><name type="personal"><namePart type="given">C. Warren</namePart><namePart type="family">Olanow</namePart><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yves</namePart><namePart type="family">Agid</namePart><affiliation>Hopital de la Salpetriere, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yoshi</namePart><namePart type="family">Mizuno</namePart><affiliation>Department of Neurology, School of Medicine, Jutendo University School of Medicine, Bunkyo‐Ku, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alberto</namePart><namePart type="family">Albanese</namePart><affiliation>Istituto Nazionale Neurologico, Milano, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">U.</namePart><namePart type="family">Bonucelli</namePart><affiliation>Department of Neuroscience, University of Pisa, Capezzano‐Pianore, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Philip</namePart><namePart type="family">Damier</namePart><affiliation>Hopital Laennec, Clinique Neurologique, Nantes, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Justo</namePart><namePart type="family">De Yebenes</namePart><affiliation>Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Oscar</namePart><namePart type="family">Gershanik</namePart><affiliation>Hopital Frances, Centro Neurold”gico, La Rioja, Buenos Aires, Argentina</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mark</namePart><namePart type="family">Guttman</namePart><affiliation>University of Toronto, Markham, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Grandas</namePart><affiliation>Hopital General G Maranon, Libertad, Velilla De San Antonio, Madrid, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mark</namePart><namePart type="family">Hallett</namePart><affiliation>Human Motor Control Section, National Institute of Neurological Disease Center, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ole</namePart><namePart type="family">Hornykiewicz</namePart><affiliation>Brain Research Institute, Vienna University Medical School, Vienna, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Jenner</namePart><affiliation>King's College London, Hodgkin Building, Guy's Campus, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Katzenschlager</namePart><affiliation>National Hospital for Neurology and Neurosurgery, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William J.</namePart><namePart type="family">Langston</namePart><affiliation>The Parkinson's Institute, Sunnyvale, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">LeWitt</namePart><affiliation>Departments of Neurology, Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, Michigan, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eldad</namePart><namePart type="family">Melamed</namePart><affiliation>Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.A.</namePart><namePart type="family">Mena</namePart><affiliation>Departmento Neurobiologia‐Investigacion, Hospital Ramon y Cajal, Ctra de Colmenar, Madrid, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.P.</namePart><namePart type="family">Michel</namePart><affiliation>Institute National de la Sante et de la Recherche Medical, Hopital de la Salpetriere, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Catherine</namePart><namePart type="family">Mytilineou</namePart><affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jose A.</namePart><namePart type="family">Obeso</namePart><affiliation>Universitarie of Navarra, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Werner</namePart><namePart type="family">Poewe</namePart><affiliation>University Hospital Innsbruck, Department of Neurology, Innsbruck, Tyrol, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Niall</namePart><namePart type="family">Quinn</namePart><affiliation>Institute of Neurology, Department of Clinical Neurology, Queen Square, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Raisman‐Vozari</namePart><affiliation>Hopital de la Salpetriere, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ali H.</namePart><namePart type="family">Rajput</namePart><affiliation>Royal University Hospital, Saskatoon, Saskatchewan, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Olivier</namePart><namePart type="family">Rascol</namePart><affiliation>Clinic University Center, Faculty of Medicine, Allees Jules‐Guesde, Toulouse, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christina</namePart><namePart type="family">Sampaio</namePart><affiliation>R Dr Antonio Loureiro Borges, Lisbon, Portugal</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Fabrizio</namePart><namePart type="family">Stocchi</namePart><affiliation>Department of Neurosciences, University of Rome, La Sapienza, San Raffaele Hospital, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="reviewArticle"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2004-09</dateIssued><dateCaptured encoding="w3cdtf">2003-08-20</dateCaptured><dateValid encoding="w3cdtf">2004-05-05</dateValid><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="references">131</extent><extent unit="words">7472</extent></physicalDescription><abstract 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</abstract><note type="funding">Novartis Pharma AG</note><note type="funding">Orion Corporation Orion Pharma</note><subject lang="en"><genre>keywords</genre><topic>Parkinson's disease</topic><topic>levodopa</topic><topic>neurotoxicity</topic><topic>dyskinesia</topic><topic>motor complications</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Research Review</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2004</date><detail type="volume"><caption>vol.</caption><number>19</number></detail><detail type="issue"><caption>no.</caption><number>9</number></detail><extent unit="pages"><start>997</start><end>1005</end><total>9</total></extent></part></relatedItem><identifier type="istex">BB30349AF852C8DA89AA6C25FC669A192C301574</identifier><identifier type="DOI">10.1002/mds.20243</identifier><identifier type="ArticleID">MDS20243</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2004 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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