The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model.
Identifieur interne : 000491 ( PubMed/Corpus ); précédent : 000490; suivant : 000492The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model.
Auteurs : Erwan Bezard ; Elsa Y. Pioli ; Qin Li ; Françoise Girard ; Vincent Mutel ; Charlotte Keywood ; Francois Tison ; Olivier Rascol ; Sonia M. PoliSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- Analysis of Variance, Animals, Antiparkinson Agents (adverse effects), Disease Models, Animal, Dose-Response Relationship, Drug, Dyskinesia, Drug-Induced (blood), Dyskinesia, Drug-Induced (drug therapy), Excitatory Amino Acid Antagonists (blood), Excitatory Amino Acid Antagonists (chemistry), Excitatory Amino Acid Antagonists (therapeutic use), Imidazoles (pharmacology), Imidazoles (therapeutic use), Levodopa (adverse effects), MPTP Poisoning (drug therapy), Macaca mulatta, Male, Motor Activity (drug effects), Pyridines (pharmacology), Pyridines (therapeutic use), Receptor, Metabotropic Glutamate 5 (metabolism), Severity of Illness Index, Time Factors.
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- blood : Dyskinesia, Drug-Induced, Excitatory Amino Acid Antagonists.
- chemical , chemistry : Excitatory Amino Acid Antagonists.
- drug effects : Motor Activity.
- drug therapy : Dyskinesia, Drug-Induced, MPTP Poisoning.
- chemical , metabolism : Receptor, Metabotropic Glutamate 5.
- chemical , pharmacology : Imidazoles, Pyridines.
- chemical , therapeutic use : Excitatory Amino Acid Antagonists, Imidazoles, Pyridines.
- Analysis of Variance, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Macaca mulatta, Male, Severity of Illness Index, Time Factors.
Abstract
Blocking metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson's disease (PD). We assessed the effect on LID of dipraglurant, a potent selective mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque model.
DOI: 10.1002/mds.25920
PubMed: 24865335
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pubmed:24865335Le document en format XML
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Pioli</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Girard, Francoise" sort="Girard, Francoise" uniqKey="Girard F" first="Françoise" last="Girard">Françoise Girard</name></author><author><name sortKey="Mutel, Vincent" sort="Mutel, Vincent" uniqKey="Mutel V" first="Vincent" last="Mutel">Vincent Mutel</name></author><author><name sortKey="Keywood, Charlotte" sort="Keywood, Charlotte" uniqKey="Keywood C" first="Charlotte" last="Keywood">Charlotte Keywood</name></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="Francois" last="Tison">Francois Tison</name></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name></author><author><name sortKey="Poli, Sonia M" sort="Poli, Sonia M" uniqKey="Poli S" first="Sonia M" last="Poli">Sonia M. Poli</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24865335</idno><idno type="pmid">24865335</idno><idno type="doi">10.1002/mds.25920</idno><idno type="wicri:Area/PubMed/Corpus">000491</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model.</title><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:affiliation>Motac neuroscience, Manchester, UK; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; Service de Neurologie, CHU de Bordeaux, Pessac, France; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Pioli, Elsa Y" sort="Pioli, Elsa Y" uniqKey="Pioli E" first="Elsa Y" last="Pioli">Elsa Y. Pioli</name></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></author><author><name sortKey="Girard, Francoise" sort="Girard, Francoise" uniqKey="Girard F" first="Françoise" last="Girard">Françoise Girard</name></author><author><name sortKey="Mutel, Vincent" sort="Mutel, Vincent" uniqKey="Mutel V" first="Vincent" last="Mutel">Vincent Mutel</name></author><author><name sortKey="Keywood, Charlotte" sort="Keywood, Charlotte" uniqKey="Keywood C" first="Charlotte" last="Keywood">Charlotte Keywood</name></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="Francois" last="Tison">Francois Tison</name></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name></author><author><name sortKey="Poli, Sonia M" sort="Poli, Sonia M" uniqKey="Poli S" first="Sonia M" last="Poli">Sonia M. Poli</name></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="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Analysis of Variance</term><term>Animals</term><term>Antiparkinson Agents (adverse effects)</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Dyskinesia, Drug-Induced (blood)</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Excitatory Amino Acid Antagonists (blood)</term><term>Excitatory Amino Acid Antagonists (chemistry)</term><term>Excitatory Amino Acid Antagonists (therapeutic use)</term><term>Imidazoles (pharmacology)</term><term>Imidazoles (therapeutic use)</term><term>Levodopa (adverse effects)</term><term>MPTP Poisoning (drug therapy)</term><term>Macaca mulatta</term><term>Male</term><term>Motor Activity (drug effects)</term><term>Pyridines (pharmacology)</term><term>Pyridines (therapeutic use)</term><term>Receptor, Metabotropic Glutamate 5 (metabolism)</term><term>Severity of Illness Index</term><term>Time Factors</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="blood" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Excitatory Amino Acid Antagonists</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Excitatory Amino Acid Antagonists</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Activity</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>MPTP Poisoning</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor, Metabotropic Glutamate 5</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Imidazoles</term><term>Pyridines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Excitatory Amino Acid Antagonists</term><term>Imidazoles</term><term>Pyridines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Analysis of Variance</term><term>Animals</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Macaca mulatta</term><term>Male</term><term>Severity of Illness Index</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Blocking metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson's disease (PD). We assessed the effect on LID of dipraglurant, a potent selective mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque model.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">24865335</PMID><DateCreated><Year>2014</Year><Month>07</Month><Day>21</Day></DateCreated><DateCompleted><Year>2015</Year><Month>03</Month><Day>30</Day></DateCompleted><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>29</Volume><Issue>8</Issue><PubDate><Year>2014</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model.</ArticleTitle><Pagination><MedlinePgn>1074-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.25920</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Blocking metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson's disease (PD). We assessed the effect on LID of dipraglurant, a potent selective mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque model.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Dipraglurant (3, 10, and 30 mg/kg, by mouth) was tested in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model of LID in a four-way crossover, single-dose, controlled study (n = 8).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Dipraglurant inhibited dyskinesias in the LID macaque model, with best effect reached at 30 mg/kg dose with no alteration of levodopa efficacy.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Acute challenges of dipraglurant were efficacious on choreic and dystonic LID in the MPTP-macaque model. Dipraglurant pharmacokinetic variables were similar to those of levodopa, suggesting that both drugs can be co-administered simultaneously in further studies.</AbstractText><CopyrightInformation>© 2014 International Parkinson and Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bezard</LastName><ForeName>Erwan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Motac neuroscience, Manchester, UK; Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; Service de Neurologie, CHU de Bordeaux, Pessac, France; Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pioli</LastName><ForeName>Elsa Y</ForeName><Initials>EY</Initials></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qin</ForeName><Initials>Q</Initials></Author><Author ValidYN="Y"><LastName>Girard</LastName><ForeName>Françoise</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Mutel</LastName><ForeName>Vincent</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Keywood</LastName><ForeName>Charlotte</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Tison</LastName><ForeName>Francois</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Rascol</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Poli</LastName><ForeName>Sonia M</ForeName><Initials>SM</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>05</Month><Day>27</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="C000596095">6-fluoro-2-(4-(pyridin-2-yl)but-3-yn-1-yl)imidazo(1,2-a)pyridine</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018691">Excitatory Amino Acid Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011725">Pyridines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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Drug-Induced</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D018691">Excitatory Amino Acid Antagonists</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000737">chemistry</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007093">Imidazoles</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="N" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007980">Levodopa</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D020267">MPTP Poisoning</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008253">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009043">Motor Activity</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011725">Pyridines</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="N" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D064529">Receptor, Metabotropic Glutamate 5</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000378">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D012720">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013997">Time Factors</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MPTP</Keyword><Keyword MajorTopicYN="N">chorea</Keyword><Keyword MajorTopicYN="N">dystonia</Keyword><Keyword MajorTopicYN="N">macaque</Keyword><Keyword MajorTopicYN="N">on-time</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>1</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>4</Month><Day>8</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>4</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="aheadofprint"><Year>2014</Year><Month>5</Month><Day>27</Day></PubMedPubDate><PubMedPubDate 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