Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over ("n-of-1") exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson's disease patients.
Identifieur interne : 000756 ( PubMed/Corpus ); précédent : 000755; suivant : 000757Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over ("n-of-1") exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson's disease patients.
Auteurs : François Tison ; Laurence Nègre-Pagès ; Wassilios G. Meissner ; Sandrine Dupouy ; Qin Li ; Marie-Laure Thiolat ; Thibaud Thiollier ; Monique Galitzky ; Fabienne Ory-Magne ; Agathe Milhet ; Laurent Marquine ; Umberto Spampinato ; Olivier Rascol ; Erwan BezardSource :
- Parkinsonism & related disorders [ 1873-5126 ] ; 2013.
English descriptors
- KwdEn :
- Adult, Aged, Animals, Antiparkinson Agents (adverse effects), Cross-Over Studies, Double-Blind Method, Dyskinesia, Drug-Induced (drug therapy), Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use), Levodopa (adverse effects), Macaca, Male, Middle Aged, Parkinson Disease (drug therapy), Parkinsonian Disorders (drug therapy), Simvastatin (therapeutic use).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- drug therapy : Dyskinesia, Drug-Induced, Parkinson Disease, Parkinsonian Disorders.
- chemical , therapeutic use : Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin.
- Adult, Aged, Animals, Cross-Over Studies, Double-Blind Method, Humans, Macaca, Male, Middle Aged.
Abstract
Simvastatin may improve levodopa-induced dyskinesia through striatal Ras-extracellular signal-regulated kinase pathway modulation.
DOI: 10.1016/j.parkreldis.2012.12.003
PubMed: 23283428
Links to Exploration step
pubmed:23283428Le document en format XML
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Meissner</name></author><author><name sortKey="Dupouy, Sandrine" sort="Dupouy, Sandrine" uniqKey="Dupouy S" first="Sandrine" last="Dupouy">Sandrine Dupouy</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Thiolat, Marie Laure" sort="Thiolat, Marie Laure" uniqKey="Thiolat M" first="Marie-Laure" last="Thiolat">Marie-Laure Thiolat</name></author><author><name sortKey="Thiollier, Thibaud" sort="Thiollier, Thibaud" uniqKey="Thiollier T" first="Thibaud" last="Thiollier">Thibaud Thiollier</name></author><author><name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name></author><author><name sortKey="Ory Magne, Fabienne" sort="Ory Magne, Fabienne" uniqKey="Ory Magne F" first="Fabienne" last="Ory-Magne">Fabienne Ory-Magne</name></author><author><name sortKey="Milhet, Agathe" sort="Milhet, Agathe" uniqKey="Milhet A" first="Agathe" last="Milhet">Agathe Milhet</name></author><author><name sortKey="Marquine, Laurent" sort="Marquine, Laurent" uniqKey="Marquine L" first="Laurent" last="Marquine">Laurent Marquine</name></author><author><name sortKey="Spampinato, Umberto" sort="Spampinato, Umberto" uniqKey="Spampinato U" first="Umberto" last="Spampinato">Umberto Spampinato</name></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23283428</idno><idno type="pmid">23283428</idno><idno type="doi">10.1016/j.parkreldis.2012.12.003</idno><idno type="wicri:Area/PubMed/Corpus">000756</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000756</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over ("n-of-1") exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson's disease patients.</title><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><nlm:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. francois.tison@chu-bordeaux.fr</nlm:affiliation></affiliation></author><author><name sortKey="Negre Pages, Laurence" sort="Negre Pages, Laurence" uniqKey="Negre Pages L" first="Laurence" last="Nègre-Pagès">Laurence Nègre-Pagès</name></author><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G" last="Meissner">Wassilios G. Meissner</name></author><author><name sortKey="Dupouy, Sandrine" sort="Dupouy, Sandrine" uniqKey="Dupouy S" first="Sandrine" last="Dupouy">Sandrine Dupouy</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Thiolat, Marie Laure" sort="Thiolat, Marie Laure" uniqKey="Thiolat M" first="Marie-Laure" last="Thiolat">Marie-Laure Thiolat</name></author><author><name sortKey="Thiollier, Thibaud" sort="Thiollier, Thibaud" uniqKey="Thiollier T" first="Thibaud" last="Thiollier">Thibaud Thiollier</name></author><author><name sortKey="Galitzky, Monique" sort="Galitzky, Monique" uniqKey="Galitzky M" first="Monique" last="Galitzky">Monique Galitzky</name></author><author><name sortKey="Ory Magne, Fabienne" sort="Ory Magne, Fabienne" uniqKey="Ory Magne F" first="Fabienne" last="Ory-Magne">Fabienne Ory-Magne</name></author><author><name sortKey="Milhet, Agathe" sort="Milhet, Agathe" uniqKey="Milhet A" first="Agathe" last="Milhet">Agathe Milhet</name></author><author><name sortKey="Marquine, Laurent" sort="Marquine, Laurent" uniqKey="Marquine L" first="Laurent" last="Marquine">Laurent Marquine</name></author><author><name sortKey="Spampinato, Umberto" sort="Spampinato, Umberto" uniqKey="Spampinato U" first="Umberto" last="Spampinato">Umberto Spampinato</name></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name></author></analytic><series><title level="j">Parkinsonism & related disorders</title><idno type="eISSN">1873-5126</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Antiparkinson Agents (adverse effects)</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Humans</term><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)</term><term>Levodopa (adverse effects)</term><term>Macaca</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Parkinsonian Disorders (drug therapy)</term><term>Simvastatin (therapeutic use)</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><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors</term><term>Simvastatin</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Humans</term><term>Macaca</term><term>Male</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Simvastatin may improve levodopa-induced dyskinesia through striatal Ras-extracellular signal-regulated kinase pathway modulation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23283428</PMID><DateCreated><Year>2013</Year><Month>03</Month><Day>22</Day></DateCreated><DateCompleted><Year>2013</Year><Month>09</Month><Day>06</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-5126</ISSN><JournalIssue CitedMedium="Internet"><Volume>19</Volume><Issue>4</Issue><PubDate><Year>2013</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Parkinsonism & related disorders</Title><ISOAbbreviation>Parkinsonism Relat. Disord.</ISOAbbreviation></Journal><ArticleTitle>Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over ("n-of-1") exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson's disease patients.</ArticleTitle><Pagination><MedlinePgn>416-21</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.parkreldis.2012.12.003</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1353-8020(12)00480-4</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Simvastatin may improve levodopa-induced dyskinesia through striatal Ras-extracellular signal-regulated kinase pathway modulation.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">(1) Six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques were assessed for parkinsonism and dyskinesia severity following acute co-administration of levodopa and simvastatin (0, 1.5, 3 and 6 mg/kg). (2) A "n-of-1" design randomized, placebo-controlled, 3 cross-over trial was then conducted in 10 Parkinson's disease patients with troublesome dyskinesia. The primary endpoint was a 7-point scale rating subjective discomfort caused by troublesome dyskinesia. Secondary endpoints related to dyskinesia severity and duration and functional impairment, severity and duration of OFF periods, motor scores and investigator- and patient-rated global impressions. (3) The pharmacodynamic variable for both studies consisted in a multiplex analysis of kinase-induced phosphorylation in T and B-lymphocytes by flow cytometry.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">(1) In the macaque, simvastatin reduced dyskinesia scores (45%), at the dose of 3 mg/kg (2) In the "n-of-1" trial no significant response was observed in the primary end point and all secondary endpoints. No serious adverse events were reported. (3) Simvastatin 3 mg/kg significantly reduce kinase-induced phosphorylation in monkeys but not simvastatin 40 mg in patients.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Simvastatin reduced dyskinesia in primates using high doses over 3 mg/kg but the exploratory trial in patients revealed no effect at 40 mg/d suggesting that higher doses, not compatible with a safe prolonged administration, are necessary.</AbstractText><CopyrightInformation>Copyright © 2012 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tison</LastName><ForeName>François</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. francois.tison@chu-bordeaux.fr</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nègre-Pagès</LastName><ForeName>Laurence</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Meissner</LastName><ForeName>Wassilios G</ForeName><Initials>WG</Initials></Author><Author ValidYN="Y"><LastName>Dupouy</LastName><ForeName>Sandrine</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qin</ForeName><Initials>Q</Initials></Author><Author ValidYN="Y"><LastName>Thiolat</LastName><ForeName>Marie-Laure</ForeName><Initials>ML</Initials></Author><Author ValidYN="Y"><LastName>Thiollier</LastName><ForeName>Thibaud</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Galitzky</LastName><ForeName>Monique</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Ory-Magne</LastName><ForeName>Fabienne</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Milhet</LastName><ForeName>Agathe</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Marquine</LastName><ForeName>Laurent</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Spampinato</LastName><ForeName>Umberto</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Rascol</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Bezard</LastName><ForeName>Erwan</ForeName><Initials>E</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>12</Month><Day>31</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Parkinsonism Relat Disord</MedlineTA><NlmUniqueID>9513583</NlmUniqueID><ISSNLinking>1353-8020</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019161">Hydroxymethylglutaryl-CoA Reductase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>AGG2FN16EV</RegistryNumber><NameOfSubstance UI="D019821">Simvastatin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><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="D018592" MajorTopicYN="N">Cross-Over Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004409" MajorTopicYN="N">Dyskinesia, Drug-Induced</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019161" MajorTopicYN="N">Hydroxymethylglutaryl-CoA Reductase Inhibitors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008251" MajorTopicYN="N">Macaca</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020734" MajorTopicYN="N">Parkinsonian Disorders</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019821" MajorTopicYN="N">Simvastatin</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>10</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2012</Year><Month>12</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2012</Year><Month>12</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>1</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>1</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>9</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23283428</ArticleId><ArticleId IdType="pii">S1353-8020(12)00480-4</ArticleId><ArticleId IdType="doi">10.1016/j.parkreldis.2012.12.003</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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