Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease
Identifieur interne : 001287 ( Main/Corpus ); précédent : 001286; suivant : 001288Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease
Auteurs : James P. Bennett Jr. ; Montford F. PierceySource :
- Journal of the Neurological Sciences [ 0022-510X ] ; 1998.
Abstract
Although l-DOPA is the current `gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D3 receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with l-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for l-DOPA treatment for several years. Thus, a new `l-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and l-DOPA is added only as necessary.
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DOI: 10.1016/S0022-510X(98)00307-4
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Bennett Jr.</name><affiliation><mods:affiliation>Professor of Neurology and Psychiatric Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel.: +1-804-924-8374; fax: +1-804-924-0370; e-mail: jpb8u@virginia.edu</mods:affiliation></affiliation></author><author><name sortKey="Piercey, Montford F" sort="Piercey, Montford F" uniqKey="Piercey M" first="Montford F" last="Piercey">Montford F. Piercey</name><affiliation><mods:affiliation>Neuroscience Department, Pharmacia and Upjohn, Kalamazoo, MI 49008, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of the Neurological Sciences</title><title level="j" type="abbrev">JNS</title><idno type="ISSN">0022-510X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998">1998</date><biblScope unit="volume">163</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="25">25</biblScope><biblScope unit="page" to="31">31</biblScope></imprint><idno type="ISSN">0022-510X</idno></series><idno type="istex">64E8777DE3B45BEB264B31C0290A4B40602DAFD5</idno><idno type="DOI">10.1016/S0022-510X(98)00307-4</idno><idno type="PII">S0022-510X(98)00307-4</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-510X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although l-DOPA is the current `gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D3 receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with l-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for l-DOPA treatment for several years. Thus, a new `l-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and l-DOPA is added only as necessary.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>James P Bennett, Jr.</name><affiliations><json:string>Professor of Neurology and Psychiatric Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA</json:string><json:string>Corresponding author. Tel.: +1-804-924-8374; fax: +1-804-924-0370; e-mail: jpb8u@virginia.edu</json:string></affiliations></json:item><json:item><name>Montford F Piercey</name><affiliations><json:string>Neuroscience Department, Pharmacia and Upjohn, Kalamazoo, MI 49008, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Pramipexole</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dopamine agonist</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Neuroprotection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Depression</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Although l-DOPA is the current `gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D3 receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with l-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for l-DOPA treatment for several years. Thus, a new `l-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and l-DOPA is added only as necessary.</abstract><qualityIndicators><score>7.273</score><pdfVersion>1.2</pdfVersion><pdfPageSize>598 x 798 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1610</abstractCharCount><pdfWordCount>4597</pdfWordCount><pdfCharCount>29949</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>223</abstractWordCount></qualityIndicators><title>Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease</title><pii><json:string>S0022-510X(98)00307-4</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>163</volume><pii><json:string>S0022-510X(00)X0067-6</json:string></pii><pages><last>31</last><first>25</first></pages><issn><json:string>0022-510X</json:string></issn><issue>1</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Journal of the Neurological Sciences</title><publicationDate>1999</publicationDate></host><categories><wos><json:string>CLINICAL NEUROLOGY</json:string><json:string>NEUROIMAGING</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>1998</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1016/S0022-510X(98)00307-4</json:string></doi><id>64E8777DE3B45BEB264B31C0290A4B40602DAFD5</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/64E8777DE3B45BEB264B31C0290A4B40602DAFD5/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/64E8777DE3B45BEB264B31C0290A4B40602DAFD5/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/64E8777DE3B45BEB264B31C0290A4B40602DAFD5/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/64E8777DE3B45BEB264B31C0290A4B40602DAFD5/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1999</date></publicationStmt><notesStmt><note type="content">Fig. 1: Structure of pramipexole.</note><note type="content">Fig. 2: Roles of dopamine receptor subtypes in regulating motor function. GABAergic inhibitory neural pathways are indicated by `−' signs at innervation sites, whereas glutamanergic excitatory pathways are indicated by `+' signs at innervation sites. Dopamine normally inhibits striatal GABAergic cells of the indirect path via D2 receptors and stimulates GABAergic cells of the direct path via D1 and D3 receptors. These effects result in inhibition of the globus pallidus internal segment (GPi or SNPR in rodents). In PD, when dopamine (DA) innervation is very low, the GPi fires at high firing rates to inhibit thalamic relay neurons and, thus, blocks thalamocortical motor pathways, resulting in bradykinesia. Pramipexole stimulates D3 receptors, which are presumed to directly inhibit GPi, removing its inhibitory gate on thalamocortical motor pathways. It also likely that it stimulates D2 receptors to indirectly inhibit GPi (SNPR). The synergy of these effects may account for pramipexole's strong recuperative effects in treating PD. GPe=globus pallidus external segment. ST=subthalamus. GPi=globus pallidus, internal segment. SNPR=substantia nigra pars reticulata.</note><note type="content">Fig. 3: Effects of pramipexole on patients with major depression. The ordinate gives the reduction in the Hamilton depression scale for placebo (PBO), 0.375, 1.0 and 5.0 mg/kg pramipexole (PPX or Mirapex®), and fluoxetine (FLU or Prozac®, 20 mg). PPX, 1.0 mg, was superior to PBO (*P<0.05), while PPX, 0.375 mg and FLU, 20 mg, were superior to PBO (P<0.10). PPX, 5 mg, had a high dropout rate due to nausea, vomiting and sedation and, thus, failed to reach statistical superiority to PBO because of the small population.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease</title><author><persName><forename type="first">James P</forename><surname>Bennett, Jr.</surname></persName><affiliation>Professor of Neurology and Psychiatric Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA</affiliation><affiliation>Corresponding author. Tel.: +1-804-924-8374; fax: +1-804-924-0370; e-mail: jpb8u@virginia.edu</affiliation></author><author><persName><forename type="first">Montford F</forename><surname>Piercey</surname></persName><affiliation>Neuroscience Department, Pharmacia and Upjohn, Kalamazoo, MI 49008, USA</affiliation></author></analytic><monogr><title level="j">Journal of the Neurological Sciences</title><title level="j" type="abbrev">JNS</title><idno type="pISSN">0022-510X</idno><idno type="PII">S0022-510X(00)X0067-6</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998"></date><biblScope unit="volume">163</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="25">25</biblScope><biblScope unit="page" to="31">31</biblScope></imprint></monogr><idno type="istex">64E8777DE3B45BEB264B31C0290A4B40602DAFD5</idno><idno type="DOI">10.1016/S0022-510X(98)00307-4</idno><idno type="PII">S0022-510X(98)00307-4</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Although l-DOPA is the current `gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D3 receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with l-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for l-DOPA treatment for several years. Thus, a new `l-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and l-DOPA is added only as necessary.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>Pramipexole</term></item><item><term>Dopamine agonist</term></item><item><term>Neuroprotection</term></item><item><term>Depression</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1998-10-21">Registration</change><change when="1998-07-23">Modified</change><change when="1998">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>JNS</jid><aid>5961</aid><ce:pii>S0022-510X(98)00307-4</ce:pii><ce:doi>10.1016/S0022-510X(98)00307-4</ce:doi><ce:copyright year="1999" type="full-transfer">Elsevier Science B.V.</ce:copyright></item-info><head><ce:title>Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease</ce:title><ce:author-group><ce:author><ce:given-name>James P</ce:given-name><ce:surname>Bennett</ce:surname><ce:suffix>Jr.</ce:suffix><ce:cross-ref refid="AFF1">a</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:author><ce:given-name>Montford F</ce:given-name><ce:surname>Piercey</ce:surname><ce:cross-ref refid="AFF2">b</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Professor of Neurology and Psychiatric Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Neuroscience Department, Pharmacia and Upjohn, Kalamazoo, MI 49008, USA</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +1-804-924-8374; fax: +1-804-924-0370; e-mail: jpb8u@virginia.edu</ce:text></ce:correspondence></ce:author-group><ce:date-received day="18" month="5" year="1998"></ce:date-received><ce:date-revised day="23" month="7" year="1998"></ce:date-revised><ce:date-accepted day="21" month="10" year="1998"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Although <ce:small-caps>l</ce:small-caps>-DOPA is the current `gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D<ce:inf>3</ce:inf> receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with <ce:small-caps>l</ce:small-caps>-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for <ce:small-caps>l</ce:small-caps>-DOPA treatment for several years. Thus, a new `<ce:small-caps>l</ce:small-caps>-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and <ce:small-caps>l</ce:small-caps>-DOPA is added only as necessary.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Parkinson's disease</ce:text></ce:keyword><ce:keyword><ce:text>Pramipexole</ce:text></ce:keyword><ce:keyword><ce:text>Dopamine agonist</ce:text></ce:keyword><ce:keyword><ce:text>Neuroprotection</ce:text></ce:keyword><ce:keyword><ce:text>Depression</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Pramipexole — a new dopamine agonist for the treatment of Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">James P</namePart><namePart type="family">Bennett, Jr.</namePart><affiliation>Professor of Neurology and Psychiatric Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA</affiliation><affiliation>Corresponding author. Tel.: +1-804-924-8374; fax: +1-804-924-0370; e-mail: jpb8u@virginia.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Montford F</namePart><namePart type="family">Piercey</namePart><affiliation>Neuroscience Department, Pharmacia and Upjohn, Kalamazoo, MI 49008, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued><dateValid encoding="w3cdtf">1998-10-21</dateValid><dateModified encoding="w3cdtf">1998-07-23</dateModified><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Although l-DOPA is the current `gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D3 receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with l-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for l-DOPA treatment for several years. Thus, a new `l-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and l-DOPA is added only as necessary.</abstract><note type="content">Fig. 1: Structure of pramipexole.</note><note type="content">Fig. 2: Roles of dopamine receptor subtypes in regulating motor function. GABAergic inhibitory neural pathways are indicated by `−' signs at innervation sites, whereas glutamanergic excitatory pathways are indicated by `+' signs at innervation sites. Dopamine normally inhibits striatal GABAergic cells of the indirect path via D2 receptors and stimulates GABAergic cells of the direct path via D1 and D3 receptors. These effects result in inhibition of the globus pallidus internal segment (GPi or SNPR in rodents). In PD, when dopamine (DA) innervation is very low, the GPi fires at high firing rates to inhibit thalamic relay neurons and, thus, blocks thalamocortical motor pathways, resulting in bradykinesia. Pramipexole stimulates D3 receptors, which are presumed to directly inhibit GPi, removing its inhibitory gate on thalamocortical motor pathways. It also likely that it stimulates D2 receptors to indirectly inhibit GPi (SNPR). The synergy of these effects may account for pramipexole's strong recuperative effects in treating PD. GPe=globus pallidus external segment. ST=subthalamus. GPi=globus pallidus, internal segment. SNPR=substantia nigra pars reticulata.</note><note type="content">Fig. 3: Effects of pramipexole on patients with major depression. The ordinate gives the reduction in the Hamilton depression scale for placebo (PBO), 0.375, 1.0 and 5.0 mg/kg pramipexole (PPX or Mirapex®), and fluoxetine (FLU or Prozac®, 20 mg). PPX, 1.0 mg, was superior to PBO (*P<0.05), while PPX, 0.375 mg and FLU, 20 mg, were superior to PBO (P<0.10). PPX, 5 mg, had a high dropout rate due to nausea, vomiting and sedation and, thus, failed to reach statistical superiority to PBO because of the small population.</note><subject><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>Pramipexole</topic><topic>Dopamine agonist</topic><topic>Neuroprotection</topic><topic>Depression</topic></subject><relatedItem type="host"><titleInfo><title>Journal of the Neurological Sciences</title></titleInfo><titleInfo type="abbreviated"><title>JNS</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">19990201</dateIssued></originInfo><identifier type="ISSN">0022-510X</identifier><identifier type="PII">S0022-510X(00)X0067-6</identifier><part><date>19990201</date><detail type="volume"><number>163</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>104</end></extent><extent unit="pages"><start>25</start><end>31</end></extent></part></relatedItem><identifier type="istex">64E8777DE3B45BEB264B31C0290A4B40602DAFD5</identifier><identifier type="DOI">10.1016/S0022-510X(98)00307-4</identifier><identifier type="PII">S0022-510X(98)00307-4</identifier><accessCondition type="use and reproduction" contentType="">© 1999Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science B.V., ©1999</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/64E8777DE3B45BEB264B31C0290A4B40602DAFD5/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">CLINICAL NEUROLOGY</classCode><classCode scheme="WOS">NEUROIMAGING</classCode><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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