Study of the antidyskinetic effect of eltoprazine in animal models of levodopa‐induced dyskinesia
Identifieur interne : 000376 ( Istex/Corpus ); précédent : 000375; suivant : 000377Study of the antidyskinetic effect of eltoprazine in animal models of levodopa‐induced dyskinesia
Auteurs : Erwan Bezard ; Elisabetta Tronci ; Elsa Y. Pioli ; Qin Li ; Gregory Porras ; Anders Björklund ; Manolo CartaSource :
- Movement Disorders [ 0885-3185 ] ; 2013-07.
Abstract
The serotonin (5‐hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l‐3,4‐dihydroxyphenylalanine (levodopa [l‐dopa])–induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5‐HT 1A/1B receptor agonist eltoprazine to counteract l‐dopa–induced dyskinesia in 6‐hydroxydopamine‐lesioned rats and in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l‐dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l‐dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine‐induced worsening of l‐dopa therapeutic effects. © 2013 Movement Disorder Society
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DOI: 10.1002/mds.25366
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Pioli</name><affiliation><mods:affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name><affiliation><mods:affiliation>Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name><affiliation><mods:affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Bjorklund, Anders" sort="Bjorklund, Anders" uniqKey="Bjorklund A" first="Anders" last="Björklund">Anders Björklund</name><affiliation><mods:affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Carta, Manolo" sort="Carta, Manolo" uniqKey="Carta M" first="Manolo" last="Carta">Manolo Carta</name><affiliation><mods:affiliation>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: manolocarta@unica.it</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>Blackwell Publishing Ltd</publisher><date type="published" when="2013-07">2013-07</date><biblScope unit="volume">28</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="1088">1088</biblScope><biblScope unit="page" to="1096">1096</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">477304D0C2C9A1C174CFD0B4EBB4AB509F72857A</idno><idno type="DOI">10.1002/mds.25366</idno><idno type="ArticleID">MDS25366</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">The serotonin (5‐hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l‐3,4‐dihydroxyphenylalanine (levodopa [l‐dopa])–induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5‐HT 1A/1B receptor agonist eltoprazine to counteract l‐dopa–induced dyskinesia in 6‐hydroxydopamine‐lesioned rats and in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l‐dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l‐dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine‐induced worsening of l‐dopa therapeutic effects. © 2013 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Erwan Bezard PhD</name><affiliations><json:string>Institute for Neurodegenerative Diseases, Bordeaux University, Bordeaux, France</json:string><json:string>Institute for Neurodegenerative Diseases, National Center for Scientific Research, Bordeaux, France</json:string><json:string>Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China</json:string></affiliations></json:item><json:item><name>Elisabetta Tronci PhD</name><affiliations><json:string>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</json:string><json:string>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</json:string></affiliations></json:item><json:item><name>Elsa Y. Pioli PhD</name><affiliations><json:string>Motac Neuroscience Ltd., Manchester, United Kingdom</json:string></affiliations></json:item><json:item><name>Qin Li PhD</name><affiliations><json:string>Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China</json:string><json:string>Motac Neuroscience Ltd., Manchester, United Kingdom</json:string></affiliations></json:item><json:item><name>Gregory Porras PhD</name><affiliations><json:string>Motac Neuroscience Ltd., Manchester, United Kingdom</json:string></affiliations></json:item><json:item><name>Anders Björklund MD</name><affiliations><json:string>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</json:string></affiliations></json:item><json:item><name>Manolo Carta PhD</name><affiliations><json:string>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</json:string><json:string>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</json:string><json:string>E-mail: manolocarta@unica.it</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>dyskinesia</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>eltoprazine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>serotonin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>amantadine</value></json:item></subject><articleId><json:string>MDS25366</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>The serotonin (5‐hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l‐3,4‐dihydroxyphenylalanine (levodopa [l‐dopa])–induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5‐HT 1A/1B receptor agonist eltoprazine to counteract l‐dopa–induced dyskinesia in 6‐hydroxydopamine‐lesioned rats and in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l‐dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l‐dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. 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xml:id="author-2"><persName><forename type="first">Elisabetta</forename><surname>Tronci</surname></persName><roleName type="degree">PhD</roleName><affiliation>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</affiliation><affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</affiliation></author><author xml:id="author-3"><persName><forename type="first">Elsa Y.</forename><surname>Pioli</surname></persName><roleName type="degree">PhD</roleName><affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</affiliation></author><author xml:id="author-4"><persName><forename type="first">Qin</forename><surname>Li</surname></persName><roleName type="degree">PhD</roleName><affiliation>Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China</affiliation><affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</affiliation></author><author xml:id="author-5"><persName><forename type="first">Gregory</forename><surname>Porras</surname></persName><roleName type="degree">PhD</roleName><affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</affiliation></author><author xml:id="author-6"><persName><forename type="first">Anders</forename><surname>Björklund</surname></persName><roleName type="degree">MD</roleName><affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</affiliation></author><author xml:id="author-7"><persName><forename type="first">Manolo</forename><surname>Carta</surname></persName><roleName type="degree">PhD</roleName><email>manolocarta@unica.it</email><affiliation>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</affiliation><affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund 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l‐3,4‐dihydroxyphenylalanine (levodopa [l‐dopa])–induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5‐HT 1A/1B receptor agonist eltoprazine to counteract l‐dopa–induced dyskinesia in 6‐hydroxydopamine‐lesioned rats and in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l‐dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l‐dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine‐induced worsening of l‐dopa therapeutic effects. © 2013 Movement Disorder Society</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>dyskinesia</term></item><item><term>levodopa</term></item><item><term>eltoprazine</term></item><item><term>serotonin</term></item><item><term>amantadine</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2012-08-24">Received</change><change when="2012-12-21">Registration</change><change when="2013-01-09">Created</change><change when="2013-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/477304D0C2C9A1C174CFD0B4EBB4AB509F72857A/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" xml:id="mds25366"><header><publicationMeta level="product"><doi origin="wiley" 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" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="80"><doi>10.1002/mds.v28.8</doi><copyright ownership="publisher">Copyright © 2013 Movement Disorder Society</copyright><numberingGroup><numbering type="journalVolume" number="28">28</numbering><numbering type="journalIssue">8</numbering></numberingGroup><coverDate startDate="2013-07">July 2013</coverDate></publicationMeta><publicationMeta level="unit" position="180" type="article" status="forIssue"><doi>10.1002/mds.25366</doi><idGroup><id type="unit" value="MDS25366"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="publisher">Copyright © 2012 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2012-08-24"></event><event type="manuscriptRevised" date="2012-12-19"></event><event type="manuscriptAccepted" date="2012-12-21"></event><event type="xmlCreated" agent="Cenveo Publisher Services" date="2013-01-09"></event><event type="publishedOnlineEarlyUnpaginated" date="2013-02-06"></event><event type="publishedOnlineFinalForm" date="2013-08-12"></event><event type="firstOnline" date="2013-02-06"></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:4.6.4 mode:FullText" date="2015-10-05"></event></eventGroup><numberingGroup><numbering type="pageFirst">1088</numbering><numbering type="pageLast">1096</numbering></numberingGroup><correspondenceTo><b>Correspondence to:</b> Dr. Manolo Carta, Department of Biomedical Sciences, Section of Physiology, Cagliari University, University Campus, 09042 Monserrato, Italy; <email>manolocarta@unica.it</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS25366.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">Study of the antidyskinetic effect of eltoprazine in animal models of levodopa‐induced dyskinesia</title><title type="short">Eltoprazine and Dyskinesia</title><title type="shortAuthors">Bezard et al.</title></titleGroup><creators><creator affiliationRef="#mds25366-aff-0001 #mds25366-aff-0002 #mds25366-aff-0003" creatorRole="author" xml:id="mds25366-cr-0001"><personName><givenNames>Erwan</givenNames><familyName>Bezard</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25366-aff-0004 #mds25366-aff-0005" creatorRole="author" xml:id="mds25366-cr-0002"><personName><givenNames>Elisabetta</givenNames><familyName>Tronci</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25366-aff-0006" creatorRole="author" xml:id="mds25366-cr-0003"><personName><givenNames>Elsa Y.</givenNames><familyName>Pioli</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25366-aff-0003 #mds25366-aff-0006" creatorRole="author" xml:id="mds25366-cr-0004"><personName><givenNames>Qin</givenNames><familyName>Li</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25366-aff-0006" creatorRole="author" xml:id="mds25366-cr-0005"><personName><givenNames>Gregory</givenNames><familyName>Porras</familyName><degrees>PhD</degrees></personName></creator><creator affiliationRef="#mds25366-aff-0005" creatorRole="author" xml:id="mds25366-cr-0006"><personName><givenNames>Anders</givenNames><familyName>Björklund</familyName><degrees>MD</degrees></personName></creator><creator affiliationRef="#mds25366-aff-0004 #mds25366-aff-0005" corresponding="yes" creatorRole="author" xml:id="mds25366-cr-0007"><personName><givenNames>Manolo</givenNames><familyName>Carta</familyName><degrees>PhD</degrees></personName></creator></creators><affiliationGroup><affiliation countryCode="FR" type="organization" xml:id="mds25366-aff-0001"><orgDiv>Institute for Neurodegenerative Diseases</orgDiv><orgName>Bordeaux University</orgName><address><city>Bordeaux</city><country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="mds25366-aff-0002"><orgDiv>Institute for Neurodegenerative Diseases</orgDiv><orgName>National Center for Scientific Research</orgName><address><city>Bordeaux</city><country>France</country></address></affiliation><affiliation countryCode="CN" type="organization" xml:id="mds25366-aff-0003"><orgDiv>Institute of Laboratory Animal Sciences</orgDiv><orgName>China Academy of Medical Sciences</orgName><address><city>Beijing</city><country>China</country></address></affiliation><affiliation countryCode="IT" type="organization" xml:id="mds25366-aff-0004"><orgDiv>Physiology Section, Department of Biomedical Sciences</orgDiv><orgName>Cagliari University</orgName><address><city>Cagliari</city><country>Italy</country></address></affiliation><affiliation countryCode="SE" type="organization" xml:id="mds25366-aff-0005"><orgDiv>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science</orgDiv><orgName>Lund University</orgName><address><city>Lund</city><country>Sweden</country></address></affiliation><affiliation countryCode="GB" type="organization" xml:id="mds25366-aff-0006"><orgName>Motac Neuroscience Ltd.</orgName><address><city>Manchester</city><country>United Kingdom</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="mds25366-kwd-0001">dyskinesia</keyword><keyword xml:id="mds25366-kwd-0002">levodopa</keyword><keyword xml:id="mds25366-kwd-0003">eltoprazine</keyword><keyword xml:id="mds25366-kwd-0004">serotonin</keyword><keyword xml:id="mds25366-kwd-0005">amantadine</keyword></keywordGroup><abstractGroup><abstract type="main"><p>The serotonin (5‐hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of <sc>l</sc>‐3,4‐dihydroxyphenylalanine (levodopa <sc>[l</sc>‐dopa])–induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5‐HT 1A/1B receptor agonist eltoprazine to counteract <sc>l</sc>‐dopa–induced dyskinesia in 6‐hydroxydopamine‐lesioned rats and in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of <sc>l</sc>‐dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the <sc>l</sc>‐dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine‐induced worsening of <sc>l</sc>‐dopa therapeutic effects. © 2013 <i>Movement</i> Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="mds25366-note-0001"><p><b>Funding agencies:</b> This study was supported by a grant from the Michael J. Fox Foundation. E.B. was also supported by grants from the Agence Nationale de la Recherche, the China Science Fund, the Seventh Framework Programme (FP7 of the European Union, France Parkinson, Fondation de France, and the Cariplo Foundation.</p></note><note xml:id="mds25366-note-0002"><p><b>Relevant conflicts of interest/financial disclosures:</b> E.B. has an equity stake in Motac Holding Ltd. and receives consultancy payments from Motac Neuroscience Ltd. E.B., Q.L., and G.P. are employees of Motac Neuroscience Ltd.</p></note><note xml:id="mds25366-note-0003"><p>Full financial disclosures and author roles may be found in the Acknowledgments section online.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Study of the antidyskinetic effect of eltoprazine in animal models of levodopa‐induced dyskinesia</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Eltoprazine and Dyskinesia</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Study of the antidyskinetic effect of eltoprazine in animal models of levodopa‐induced dyskinesia</title></titleInfo><name type="personal"><namePart type="given">Erwan</namePart><namePart type="family">Bezard</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute for Neurodegenerative Diseases, Bordeaux University, Bordeaux, France</affiliation><affiliation>Institute for Neurodegenerative Diseases, National Center for Scientific Research, Bordeaux, France</affiliation><affiliation>Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elisabetta</namePart><namePart type="family">Tronci</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</affiliation><affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elsa Y.</namePart><namePart type="family">Pioli</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Qin</namePart><namePart type="family">Li</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China</affiliation><affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gregory</namePart><namePart type="family">Porras</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Motac Neuroscience Ltd., Manchester, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anders</namePart><namePart type="family">Björklund</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Manolo</namePart><namePart type="family">Carta</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Physiology Section, Department of Biomedical Sciences, Cagliari University, Cagliari, Italy</affiliation><affiliation>Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden</affiliation><affiliation>E-mail: manolocarta@unica.it</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2013-07</dateIssued><dateCreated encoding="w3cdtf">2013-01-09</dateCreated><dateCaptured encoding="w3cdtf">2012-08-24</dateCaptured><dateValid encoding="w3cdtf">2012-12-21</dateValid><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>The serotonin (5‐hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l‐3,4‐dihydroxyphenylalanine (levodopa [l‐dopa])–induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5‐HT 1A/1B receptor agonist eltoprazine to counteract l‐dopa–induced dyskinesia in 6‐hydroxydopamine‐lesioned rats and in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l‐dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l‐dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine‐induced worsening of l‐dopa therapeutic effects. © 2013 Movement Disorder Society</abstract><subject><genre>keywords</genre><topic>dyskinesia</topic><topic>levodopa</topic><topic>eltoprazine</topic><topic>serotonin</topic><topic>amantadine</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 Article</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>2013</date><detail type="volume"><caption>vol.</caption><number>28</number></detail><detail type="issue"><caption>no.</caption><number>8</number></detail><extent unit="pages"><start>1088</start><end>1096</end><total>9</total></extent></part></relatedItem><identifier type="istex">477304D0C2C9A1C174CFD0B4EBB4AB509F72857A</identifier><identifier type="DOI">10.1002/mds.25366</identifier><identifier type="ArticleID">MDS25366</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2013 Movement Disorder SocietyCopyright © 2012 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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