Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease
Identifieur interne : 002407 ( Istex/Corpus ); précédent : 002406; suivant : 002408Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease
Auteurs : William Bara-Jimenez ; Francesco Bibbiani ; Michael J. Morris ; Tzvetelina Dimitrova ; Abdullah Sherzai ; Maral M. Mouradian ; Thomas N. ChaseSource :
- Movement Disorders [ 0885-3185 ] ; 2005-08.
English descriptors
Abstract
Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5‐HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5‐HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3‐week, double‐blind, placebo‐controlled, proof‐of‐concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa‐induced dyskinesias and prolonged its antiparkinsonian response (P ≤ 0.05). Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society
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DOI: 10.1002/mds.20370
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ISTEX:5344FB0941453C52FC59B0697C4054DC8A6E6412Le document en format XML
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With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5‐HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5‐HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3‐week, double‐blind, placebo‐controlled, proof‐of‐concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa‐induced dyskinesias and prolonged its antiparkinsonian response (P ≤ 0.05). Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>William Bara‐Jimenez MD</name><affiliations><json:string>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</json:string></affiliations></json:item><json:item><name>Francesco Bibbiani MD</name><affiliations><json:string>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</json:string></affiliations></json:item><json:item><name>Michael J. 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With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5‐HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5‐HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3‐week, double‐blind, placebo‐controlled, proof‐of‐concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa‐induced dyskinesias and prolonged its antiparkinsonian response (P ≤ 0.05). Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society</abstract><qualityIndicators><score>5.066</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1359</abstractCharCount><pdfWordCount>2942</pdfWordCount><pdfCharCount>19606</pdfCharCount><pdfPageCount>5</pdfPageCount><abstractWordCount>177</abstractWordCount></qualityIndicators><title>Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease</title><genre><json:string>Serial article</json:string></genre><host><volume>20</volume><pages><total>5</total><last>936</last><first>932</first></pages><issn><json:string>0885-3185</json:string></issn><issue>8</issue><subject><json:item><value>Research 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Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>5‐HT1A receptor</term></item><item><term>serotonin</term></item><item><term>dopamine</term></item><item><term>Parkinson's disease</term></item><item><term>dyskinesias, levodopa</term></item><item><term>striatum</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="2004-04-21">Received</change><change when="2004-09-22">Registration</change><change when="2005-08">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/5344FB0941453C52FC59B0697C4054DC8A6E6412/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="subtitle">Official Journal of the Movement Disorder Society</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="80"><doi origin="wiley" registered="yes">10.1002/mds.v20:8</doi><numberingGroup><numbering type="journalVolume" number="20">20</numbering><numbering type="journalIssue">8</numbering></numberingGroup><coverDate startDate="2005-08">August 2005</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="30" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.20370</doi><idGroup><id type="unit" value="MDS20370"></id></idGroup><countGroup><count type="pageTotal" number="5"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2005 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2004-04-21"></event><event type="manuscriptRevised" date="2004-08-27"></event><event type="manuscriptAccepted" date="2004-09-22"></event><event type="publishedOnlineEarlyUnpaginated" date="2005-03-24"></event><event type="firstOnline" date="2005-03-24"></event><event type="publishedOnlineFinalForm" date="2005-07-28"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-03-09"></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">932</numbering><numbering type="pageLast">936</numbering></numberingGroup><correspondenceTo>Bldg. 10, Rm. 5C103, National Institutes of Health, Bethesda, MD 20892</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS20370.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="32"></count><count type="wordTotal" number="3256"></count></countGroup><titleGroup><title type="main" xml:lang="en">Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease</title><title type="short" xml:lang="en">5‐HT1A Agonist Effects in Parkinson's Disease</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>William</givenNames><familyName>Bara‐Jimenez</familyName><degrees>MD</degrees></personName><contactDetails><email>Baraw@ninds.nih.gov</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Francesco</givenNames><familyName>Bibbiani</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael J.</givenNames><familyName>Morris</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Tzvetelina</givenNames><familyName>Dimitrova</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Abdullah</givenNames><familyName>Sherzai</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Maral M.</givenNames><familyName>Mouradian</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Thomas N.</givenNames><familyName>Chase</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">5‐HT1A receptor</keyword><keyword xml:id="kwd2">serotonin</keyword><keyword xml:id="kwd3">dopamine</keyword><keyword xml:id="kwd4">Parkinson's disease</keyword><keyword xml:id="kwd5">dyskinesias, levodopa</keyword><keyword xml:id="kwd6">striatum</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5‐HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5‐HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3‐week, double‐blind, placebo‐controlled, proof‐of‐concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa‐induced dyskinesias and prolonged its antiparkinsonian response (<i>P</i> ≤ 0.05). Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>5‐HT1A Agonist Effects in Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">William</namePart><namePart type="family">Bara‐Jimenez</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><description>Correspondence: Bldg. 10, Rm. 5C103, National Institutes of Health, Bethesda, MD 20892</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Francesco</namePart><namePart type="family">Bibbiani</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael J.</namePart><namePart type="family">Morris</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tzvetelina</namePart><namePart type="family">Dimitrova</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Abdullah</namePart><namePart type="family">Sherzai</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maral M.</namePart><namePart type="family">Mouradian</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas N.</namePart><namePart type="family">Chase</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2005-08</dateIssued><dateCaptured encoding="w3cdtf">2004-04-21</dateCaptured><dateValid encoding="w3cdtf">2004-09-22</dateValid><copyrightDate encoding="w3cdtf">2005</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="figures">2</extent><extent unit="references">32</extent><extent unit="words">3256</extent></physicalDescription><abstract lang="en">Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5‐HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5‐HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3‐week, double‐blind, placebo‐controlled, proof‐of‐concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa‐induced dyskinesias and prolonged its antiparkinsonian response (P ≤ 0.05). Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society</abstract><subject lang="en"><genre>Keywords</genre><topic>5‐HT1A receptor</topic><topic>serotonin</topic><topic>dopamine</topic><topic>Parkinson's disease</topic><topic>dyskinesias, levodopa</topic><topic>striatum</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><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>2005</date><detail type="volume"><caption>vol.</caption><number>20</number></detail><detail type="issue"><caption>no.</caption><number>8</number></detail><extent unit="pages"><start>932</start><end>936</end><total>5</total></extent></part></relatedItem><identifier type="istex">5344FB0941453C52FC59B0697C4054DC8A6E6412</identifier><identifier type="DOI">10.1002/mds.20370</identifier><identifier type="ArticleID">MDS20370</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2005 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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