New treatments for levodopa-induced motor complications.
Identifieur interne : 000298 ( PubMed/Curation ); précédent : 000297; suivant : 000299New treatments for levodopa-induced motor complications.
Auteurs : Olivier Rascol [France] ; Santiago Perez-Lloret ; Joaquim J. Ferreira [Portugal]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2015.
English descriptors
- KwdEn :
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- drug therapy : Dyskinesia, Drug-Induced, Parkinson Disease.
- etiology : Dyskinesia, Drug-Induced.
- Animals, Humans.
Abstract
Levodopa (l-dopa)-induced motor complications, including motor fluctuations and dyskinesia, affect almost all patients with Parkinson's disease (PD) at some point during the disease course, with relevant implications in global health status. Various dopaminergic and nondopaminergic pharmacological approaches as well as more invasive strategies including devices and functional surgery are available to manage such complications. In spite of undisputable improvements during the last decades, many patients remain significantly disabled, and a fully satisfying management of l-dopa-induced motor complications is still an important unmet need of PD therapy. This article reviews the recent trial results published from 2013 to April 2015 about pharmacological and nonpharmacological interventions to treat motor complications. Randomized controlled trials conducted in patients suffering from already established complications showed that new levodopa (l-dopa) formulations such as intrajejunal l-dopa-carbidopa infusion and bilayered extended-release l-dopa-carbidopa (IPX066) can improve motor fluctuations. Positive results were also obtained with a new monoamine oxidase B (MAO-B) inhibitor (safinamide) and a catechol-O-methyltransferase COMT inhibitor (opicapone). Pilot data suggest that new formulations of dopamine agonists (inhaled apomorphine) are also of potential interest. The development of novel nondopaminergic adenosine A2A antagonists (istradefylline, preladenant, and tozadenant) to treat motor fluctuations showed conflicting results in phase 2 and phase 3 trials. For dyskinesia, trials with new amantadine extended-release formulations confirmed the interest of the glutamatergic N-methyl-d-aspartate (NMDA) antagonist approach. Positive pilot antidyskinetic effects were also recently reported using serotonin agents such as eltoprazine and glutamate mGluR5 modulators such as mavoglurant. However, the translation to clinical practice of such innovative concepts remains challenging, because subsequent phase 2 trials conducted to confirm the antidyskynetic effects of mavoglurant failed, leading to the interruption of the development of this compound for this indication.
DOI: 10.1002/mds.26362
PubMed: 26293004
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Santiago Perez-Lloret<affiliation><nlm:affiliation>Laboratory of Epidemiology and Experimental Pharmacology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA).</nlm:affiliation><wicri:noCountry code="subField">Pontifical Catholic University of Argentina (UCA)</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">New treatments for levodopa-induced motor complications.</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Pharmacology and Neurosciences, University Hospital and University of Toulouse 3, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Clinical Pharmacology and Neurosciences, University Hospital and University of Toulouse 3</wicri:regionArea></affiliation></author><author><name sortKey="Perez Lloret, Santiago" sort="Perez Lloret, Santiago" uniqKey="Perez Lloret S" first="Santiago" last="Perez-Lloret">Santiago Perez-Lloret</name><affiliation><nlm:affiliation>Laboratory of Epidemiology and Experimental Pharmacology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA).</nlm:affiliation><wicri:noCountry code="subField">Pontifical Catholic University of Argentina (UCA)</wicri:noCountry></affiliation></author><author><name sortKey="Ferreira, Joaquim J" sort="Ferreira, Joaquim J" uniqKey="Ferreira J" first="Joaquim J" last="Ferreira">Joaquim J. Ferreira</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26293004</idno><idno type="pmid">26293004</idno><idno type="doi">10.1002/mds.26362</idno><idno type="wicri:Area/PubMed/Corpus">000299</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000299</idno><idno type="wicri:Area/PubMed/Curation">000298</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000298</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">New treatments for levodopa-induced motor complications.</title><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Pharmacology and Neurosciences, University Hospital and University of Toulouse 3, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Clinical Pharmacology and Neurosciences, University Hospital and University of Toulouse 3</wicri:regionArea></affiliation></author><author><name sortKey="Perez Lloret, Santiago" sort="Perez Lloret, Santiago" uniqKey="Perez Lloret S" first="Santiago" last="Perez-Lloret">Santiago Perez-Lloret</name><affiliation><nlm:affiliation>Laboratory of Epidemiology and Experimental Pharmacology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA).</nlm:affiliation><wicri:noCountry code="subField">Pontifical Catholic University of Argentina (UCA)</wicri:noCountry></affiliation></author><author><name sortKey="Ferreira, Joaquim J" sort="Ferreira, Joaquim J" uniqKey="Ferreira J" first="Joaquim J" last="Ferreira">Joaquim J. Ferreira</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal.</nlm:affiliation><country xml:lang="fr">Portugal</country><wicri:regionArea>Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon</wicri:regionArea></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiparkinson Agents (adverse effects)</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Humans</term><term>Levodopa (adverse effects)</term><term>Parkinson Disease (drug therapy)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Levodopa (l-dopa)-induced motor complications, including motor fluctuations and dyskinesia, affect almost all patients with Parkinson's disease (PD) at some point during the disease course, with relevant implications in global health status. Various dopaminergic and nondopaminergic pharmacological approaches as well as more invasive strategies including devices and functional surgery are available to manage such complications. In spite of undisputable improvements during the last decades, many patients remain significantly disabled, and a fully satisfying management of l-dopa-induced motor complications is still an important unmet need of PD therapy. This article reviews the recent trial results published from 2013 to April 2015 about pharmacological and nonpharmacological interventions to treat motor complications. Randomized controlled trials conducted in patients suffering from already established complications showed that new levodopa (l-dopa) formulations such as intrajejunal l-dopa-carbidopa infusion and bilayered extended-release l-dopa-carbidopa (IPX066) can improve motor fluctuations. Positive results were also obtained with a new monoamine oxidase B (MAO-B) inhibitor (safinamide) and a catechol-O-methyltransferase COMT inhibitor (opicapone). Pilot data suggest that new formulations of dopamine agonists (inhaled apomorphine) are also of potential interest. The development of novel nondopaminergic adenosine A2A antagonists (istradefylline, preladenant, and tozadenant) to treat motor fluctuations showed conflicting results in phase 2 and phase 3 trials. For dyskinesia, trials with new amantadine extended-release formulations confirmed the interest of the glutamatergic N-methyl-d-aspartate (NMDA) antagonist approach. Positive pilot antidyskinetic effects were also recently reported using serotonin agents such as eltoprazine and glutamate mGluR5 modulators such as mavoglurant. However, the translation to clinical practice of such innovative concepts remains challenging, because subsequent phase 2 trials conducted to confirm the antidyskynetic effects of mavoglurant failed, leading to the interruption of the development of this compound for this indication.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26293004</PMID><DateCreated><Year>2015</Year><Month>09</Month><Day>16</Day></DateCreated><DateCompleted><Year>2016</Year><Month>06</Month><Day>09</Day></DateCompleted><DateRevised><Year>2015</Year><Month>09</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>30</Volume><Issue>11</Issue><PubDate><Year>2015</Year><Month>Sep</Month><Day>15</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>New treatments for levodopa-induced motor complications.</ArticleTitle><Pagination><MedlinePgn>1451-60</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.26362</ELocationID><Abstract><AbstractText>Levodopa (l-dopa)-induced motor complications, including motor fluctuations and dyskinesia, affect almost all patients with Parkinson's disease (PD) at some point during the disease course, with relevant implications in global health status. Various dopaminergic and nondopaminergic pharmacological approaches as well as more invasive strategies including devices and functional surgery are available to manage such complications. In spite of undisputable improvements during the last decades, many patients remain significantly disabled, and a fully satisfying management of l-dopa-induced motor complications is still an important unmet need of PD therapy. This article reviews the recent trial results published from 2013 to April 2015 about pharmacological and nonpharmacological interventions to treat motor complications. Randomized controlled trials conducted in patients suffering from already established complications showed that new levodopa (l-dopa) formulations such as intrajejunal l-dopa-carbidopa infusion and bilayered extended-release l-dopa-carbidopa (IPX066) can improve motor fluctuations. Positive results were also obtained with a new monoamine oxidase B (MAO-B) inhibitor (safinamide) and a catechol-O-methyltransferase COMT inhibitor (opicapone). Pilot data suggest that new formulations of dopamine agonists (inhaled apomorphine) are also of potential interest. The development of novel nondopaminergic adenosine A2A antagonists (istradefylline, preladenant, and tozadenant) to treat motor fluctuations showed conflicting results in phase 2 and phase 3 trials. For dyskinesia, trials with new amantadine extended-release formulations confirmed the interest of the glutamatergic N-methyl-d-aspartate (NMDA) antagonist approach. Positive pilot antidyskinetic effects were also recently reported using serotonin agents such as eltoprazine and glutamate mGluR5 modulators such as mavoglurant. However, the translation to clinical practice of such innovative concepts remains challenging, because subsequent phase 2 trials conducted to confirm the antidyskynetic effects of mavoglurant failed, leading to the interruption of the development of this compound for this indication.</AbstractText><CopyrightInformation>© 2015 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rascol</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Clinical Pharmacology and Neurosciences, University Hospital and University of Toulouse 3, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM CIC1436 and UMR825, Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perez-Lloret</LastName><ForeName>Santiago</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Laboratory of Epidemiology and Experimental Pharmacology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA).</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferreira</LastName><ForeName>Joaquim J</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>08</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000978" MajorTopicYN="N">Antiparkinson Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004409" MajorTopicYN="N">Dyskinesia, Drug-Induced</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">dyskinesias</Keyword><Keyword MajorTopicYN="N">levodopa</Keyword><Keyword MajorTopicYN="N">motor fluctuations</Keyword><Keyword MajorTopicYN="N">pharmacotherapy</Keyword><Keyword MajorTopicYN="N">wearing-off</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>06</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>07</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>8</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>8</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>6</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26293004</ArticleId><ArticleId IdType="doi">10.1002/mds.26362</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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