Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies.
Identifieur interne : 002D08 ( PubMed/Curation ); précédent : 002D07; suivant : 002D09Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies.
Auteurs : Kaveh M. Koochesfahani [Canada] ; Raúl De La Fuente-Fernández ; Vesna Sossi ; Michael Schulzer ; Lakshmi N. Yatham ; Thomas J. Ruth ; Stephan Blinder ; A Jon StoesslSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2006.
English descriptors
- KwdEn :
- Administration, Oral, Adult, Aged, Basal Ganglia (drug effects), Basal Ganglia (radionuclide imaging), Caudate Nucleus (drug effects), Caudate Nucleus (radionuclide imaging), Central Nervous System Stimulants (administration & dosage), Dopamine (metabolism), Dopamine D2 Receptor Antagonists, Dopamine Plasma Membrane Transport Proteins (antagonists & inhibitors), Extracellular Fluid (drug effects), Female, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Male, Methylphenidate (administration & dosage), Middle Aged, Parkinson Disease (drug therapy), Parkinson Disease (radionuclide imaging), Positron-Emission Tomography, Putamen (drug effects), Putamen (radionuclide imaging), Raclopride (diagnostic use), Raclopride (pharmacokinetics), Treatment Failure.
- MESH :
- chemical , administration & dosage : Central Nervous System Stimulants, Methylphenidate.
- chemical , antagonists & inhibitors : Dopamine Plasma Membrane Transport Proteins.
- chemical , diagnostic use : Raclopride.
- drug effects : Basal Ganglia, Caudate Nucleus, Extracellular Fluid, Putamen.
- drug therapy : Parkinson Disease.
- chemical , metabolism : Dopamine.
- chemical , pharmacokinetics : Raclopride.
- radionuclide imaging : Basal Ganglia, Caudate Nucleus, Parkinson Disease, Putamen.
- Administration, Oral, Adult, Aged, Dopamine D2 Receptor Antagonists, Female, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Male, Middle Aged, Positron-Emission Tomography, Treatment Failure.
Abstract
In this study, we assessed the changes of endogenous dopamine (DA) levels in response to methylphenidate in 5 patients with idiopathic Parkinson's disease (PD) and 6 healthy controls. Three-dimensional positron emission tomography was performed with the D2 receptor antagonist [11C]raclopride (RAC) at baseline and 1 hour following the administration of oral methylphenidate (0.8 mg/kg) to assess changes in dopamine levels indirectly. Oral methylphenidate produced no significant change in extracellular DA levels in the putamen, as estimated by comparing changes in RAC binding at baseline and 1 hour following its administration in PD subjects and healthy controls. However, there were small changes in RAC binding of opposite direction in caudate and ventral striatal regions compared between the two groups. Although there was no consistent improvement in motor function in the PD group, some patients did experience a subjective high in response to methylphenidate (MP). Failure of oral MP to alter extracellular DA levels in putamen could result from degeneration of presynaptic dopaminergic terminals, with consequent severe reductions in the levels of endogenous DA and dopamine transporter in PD subjects. Our data provide in vivo neurochemical support for the lack of clinical efficacy following MP in PD patients and are also in keeping with reduced DA release following amphetamine in PD subjects.
DOI: 10.1002/mds.20857
PubMed: 16570297
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Koochesfahani</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. kavehm@interchange.ubc.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea></affiliation></author><author><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name></author><author><name sortKey="Yatham, Lakshmi N" sort="Yatham, Lakshmi N" uniqKey="Yatham L" first="Lakshmi N" last="Yatham">Lakshmi N. Yatham</name></author><author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J" last="Ruth">Thomas J. Ruth</name></author><author><name sortKey="Blinder, Stephan" sort="Blinder, Stephan" uniqKey="Blinder S" first="Stephan" last="Blinder">Stephan Blinder</name></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="doi">10.1002/mds.20857</idno><idno type="RBID">pubmed:16570297</idno><idno type="pmid">16570297</idno><idno type="wicri:Area/PubMed/Corpus">002D08</idno><idno type="wicri:Area/PubMed/Curation">002D08</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies.</title><author><name sortKey="Koochesfahani, Kaveh M" sort="Koochesfahani, Kaveh M" uniqKey="Koochesfahani K" first="Kaveh M" last="Koochesfahani">Kaveh M. Koochesfahani</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. kavehm@interchange.ubc.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia</wicri:regionArea></affiliation></author><author><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name></author><author><name sortKey="Yatham, Lakshmi N" sort="Yatham, Lakshmi N" uniqKey="Yatham L" first="Lakshmi N" last="Yatham">Lakshmi N. Yatham</name></author><author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J" last="Ruth">Thomas J. Ruth</name></author><author><name sortKey="Blinder, Stephan" sort="Blinder, Stephan" uniqKey="Blinder S" first="Stephan" last="Blinder">Stephan Blinder</name></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Oral</term><term>Adult</term><term>Aged</term><term>Basal Ganglia (drug effects)</term><term>Basal Ganglia (radionuclide imaging)</term><term>Caudate Nucleus (drug effects)</term><term>Caudate Nucleus (radionuclide imaging)</term><term>Central Nervous System Stimulants (administration & dosage)</term><term>Dopamine (metabolism)</term><term>Dopamine D2 Receptor Antagonists</term><term>Dopamine Plasma Membrane Transport Proteins (antagonists & inhibitors)</term><term>Extracellular Fluid (drug effects)</term><term>Female</term><term>Humans</term><term>Image Processing, Computer-Assisted</term><term>Imaging, Three-Dimensional</term><term>Male</term><term>Methylphenidate (administration & dosage)</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (radionuclide imaging)</term><term>Positron-Emission Tomography</term><term>Putamen (drug effects)</term><term>Putamen (radionuclide imaging)</term><term>Raclopride (diagnostic use)</term><term>Raclopride (pharmacokinetics)</term><term>Treatment Failure</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Central Nervous System Stimulants</term><term>Methylphenidate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Dopamine Plasma Membrane Transport Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Raclopride</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Basal Ganglia</term><term>Caudate Nucleus</term><term>Extracellular Fluid</term><term>Putamen</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Raclopride</term></keywords><keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Basal Ganglia</term><term>Caudate Nucleus</term><term>Parkinson Disease</term><term>Putamen</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term><term>Adult</term><term>Aged</term><term>Dopamine D2 Receptor Antagonists</term><term>Female</term><term>Humans</term><term>Image Processing, Computer-Assisted</term><term>Imaging, Three-Dimensional</term><term>Male</term><term>Middle Aged</term><term>Positron-Emission Tomography</term><term>Treatment Failure</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In this study, we assessed the changes of endogenous dopamine (DA) levels in response to methylphenidate in 5 patients with idiopathic Parkinson's disease (PD) and 6 healthy controls. Three-dimensional positron emission tomography was performed with the D2 receptor antagonist [11C]raclopride (RAC) at baseline and 1 hour following the administration of oral methylphenidate (0.8 mg/kg) to assess changes in dopamine levels indirectly. Oral methylphenidate produced no significant change in extracellular DA levels in the putamen, as estimated by comparing changes in RAC binding at baseline and 1 hour following its administration in PD subjects and healthy controls. However, there were small changes in RAC binding of opposite direction in caudate and ventral striatal regions compared between the two groups. Although there was no consistent improvement in motor function in the PD group, some patients did experience a subjective high in response to methylphenidate (MP). Failure of oral MP to alter extracellular DA levels in putamen could result from degeneration of presynaptic dopaminergic terminals, with consequent severe reductions in the levels of endogenous DA and dopamine transporter in PD subjects. Our data provide in vivo neurochemical support for the lack of clinical efficacy following MP in PD patients and are also in keeping with reduced DA release following amphetamine in PD subjects.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">16570297</PMID><DateCreated><Year>2006</Year><Month>08</Month><Day>28</Day></DateCreated><DateCompleted><Year>2006</Year><Month>12</Month><Day>15</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>21</Volume><Issue>7</Issue><PubDate><Year>2006</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies.</ArticleTitle><Pagination><MedlinePgn>970-5</MedlinePgn></Pagination><Abstract><AbstractText>In this study, we assessed the changes of endogenous dopamine (DA) levels in response to methylphenidate in 5 patients with idiopathic Parkinson's disease (PD) and 6 healthy controls. Three-dimensional positron emission tomography was performed with the D2 receptor antagonist [11C]raclopride (RAC) at baseline and 1 hour following the administration of oral methylphenidate (0.8 mg/kg) to assess changes in dopamine levels indirectly. Oral methylphenidate produced no significant change in extracellular DA levels in the putamen, as estimated by comparing changes in RAC binding at baseline and 1 hour following its administration in PD subjects and healthy controls. However, there were small changes in RAC binding of opposite direction in caudate and ventral striatal regions compared between the two groups. Although there was no consistent improvement in motor function in the PD group, some patients did experience a subjective high in response to methylphenidate (MP). Failure of oral MP to alter extracellular DA levels in putamen could result from degeneration of presynaptic dopaminergic terminals, with consequent severe reductions in the levels of endogenous DA and dopamine transporter in PD subjects. Our data provide in vivo neurochemical support for the lack of clinical efficacy following MP in PD patients and are also in keeping with reduced DA release following amphetamine in PD subjects.</AbstractText><CopyrightInformation>(c) 2006 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Koochesfahani</LastName><ForeName>Kaveh M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. kavehm@interchange.ubc.ca</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de la Fuente-Fernández</LastName><ForeName>Raúl</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Sossi</LastName><ForeName>Vesna</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Schulzer</LastName><ForeName>Michael</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Yatham</LastName><ForeName>Lakshmi N</ForeName><Initials>LN</Initials></Author><Author ValidYN="Y"><LastName>Ruth</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials></Author><Author ValidYN="Y"><LastName>Blinder</LastName><ForeName>Stephan</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Stoessl</LastName><ForeName>A Jon</ForeName><Initials>AJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D018848">Controlled Clinical Trial</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></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="D000697">Central Nervous System Stimulants</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D065127">Dopamine D2 Receptor Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050483">Dopamine Plasma Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>207ZZ9QZ49</RegistryNumber><NameOfSubstance UI="D008774">Methylphenidate</NameOfSubstance></Chemical><Chemical><RegistryNumber>430K3SOZ7G</RegistryNumber><NameOfSubstance UI="D020891">Raclopride</NameOfSubstance></Chemical><Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber><NameOfSubstance UI="D004298">Dopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000284">Administration, Oral</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001479">Basal Ganglia</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000531">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002421">Caudate Nucleus</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000531">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000697">Central Nervous System Stimulants</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000008">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004298">Dopamine</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000378">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D065127">Dopamine D2 Receptor Antagonists</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D050483">Dopamine Plasma Membrane Transport Proteins</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000037">antagonists & inhibitors</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D045604">Extracellular Fluid</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000187">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D007091">Image Processing, Computer-Assisted</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D021621">Imaging, Three-Dimensional</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008774">Methylphenidate</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000008">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000531">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D049268">Positron-Emission Tomography</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011699">Putamen</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000531">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D020891">Raclopride</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000176">diagnostic use</QualifierName><QualifierName MajorTopicYN="N" UI="Q000493">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017211">Treatment Failure</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>3</Month><Day>30</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>12</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>3</Month><Day>30</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.20857</ArticleId><ArticleId 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