Is levodopa toxic to human substantia nigra?
Identifieur interne : 004614 ( PubMed/Corpus ); précédent : 004613; suivant : 004615Is levodopa toxic to human substantia nigra?
Auteurs : A H Rajput ; M E Fenton ; S. Birdi ; R. MacaulaySource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1997.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Child, Dystonia (drug therapy), Female, Humans, Levodopa (administration & dosage), Levodopa (adverse effects), Male, Middle Aged, Parkinson Disease (drug therapy), Substantia Nigra (drug effects), Substantia Nigra (pathology), Substantia Nigra (physiopathology), Time Factors, Tomography, Emission-Computed, Tremor (drug therapy).
- MESH :
- chemical , administration & dosage : Levodopa.
- chemical , adverse effects : Levodopa.
- drug effects : Substantia Nigra.
- drug therapy : Dystonia, Parkinson Disease, Tremor.
- pathology : Substantia Nigra.
- physiopathology : Substantia Nigra.
- Adult, Aged, Aged, 80 and over, Child, Female, Humans, Male, Middle Aged, Time Factors, Tomography, Emission-Computed.
Abstract
Levodopa (LD) is the most effective drug for symptomatic control of Parkinson's disease, but has been suspected to be toxic to substantia nigra (SN) dopaminergic neurons. Tissue culture and animal studies of LD toxicity have produced contradictory evidence, and one study reported that a human subject exposed to a large cumulative dose (cd) of LD over 4 years had no evidence of SN damage. We report the cases of five patients, each of whom received a large cd of LD over a long period. Fluorodopa positron-emission tomography performed in one case indicated parkinsonism. Autopsies in two cases indicated a normal SN in one and a hypopigmented SN with normal cell complement in the other. Three patients had essential tremor, one had nonprogressive parkinsonism, and one had dopa-responsive dystonia. LD (without decarboxylase inhibitor) was administered over 21 years (cd = 21.99 kg), 9 years (cd = 6.6 kg), 26 years (cd = 18.7 kg), 11 years (cd = 3 kg), and 26 years (cd = 23.93 kg), respectively. None of the patients with essential tremor developed clinical features of parkinsonism that indicated significant SN damage, and one had a normal SN at autopsy. The parkinsonian patient displayed no detectable acceleration of disease process, and the patient with dopa-responsive dystonia had a normal complement of SN neurons at autopsy. We conclude that LD, administered at a dose commonly used for treating Parkinson's disease, was not toxic to SN neurons in these cases.
DOI: 10.1002/mds.870120503
PubMed: 9380042
Links to Exploration step
pubmed:9380042Le document en format XML
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Macaulay</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1997">1997</date><idno type="RBID">pubmed:9380042</idno><idno type="pmid">9380042</idno><idno type="doi">10.1002/mds.870120503</idno><idno type="wicri:Area/PubMed/Corpus">004614</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Is levodopa toxic to human substantia nigra?</title><author><name sortKey="Rajput, A H" sort="Rajput, A H" uniqKey="Rajput A" first="A H" last="Rajput">A H Rajput</name><affiliation><nlm:affiliation>Division of Neurology, Royal University Hospital, Saskatoon, Saskatchewan, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Fenton, M E" sort="Fenton, M E" uniqKey="Fenton M" first="M E" last="Fenton">M E Fenton</name></author><author><name sortKey="Birdi, S" sort="Birdi, S" uniqKey="Birdi S" first="S" last="Birdi">S. Birdi</name></author><author><name sortKey="Macaulay, R" sort="Macaulay, R" uniqKey="Macaulay R" first="R" last="Macaulay">R. Macaulay</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="1997" type="published">1997</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Child</term><term>Dystonia (drug therapy)</term><term>Female</term><term>Humans</term><term>Levodopa (administration & dosage)</term><term>Levodopa (adverse effects)</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (pathology)</term><term>Substantia Nigra (physiopathology)</term><term>Time Factors</term><term>Tomography, Emission-Computed</term><term>Tremor (drug therapy)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dystonia</term><term>Parkinson Disease</term><term>Tremor</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Child</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Time Factors</term><term>Tomography, Emission-Computed</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Levodopa (LD) is the most effective drug for symptomatic control of Parkinson's disease, but has been suspected to be toxic to substantia nigra (SN) dopaminergic neurons. Tissue culture and animal studies of LD toxicity have produced contradictory evidence, and one study reported that a human subject exposed to a large cumulative dose (cd) of LD over 4 years had no evidence of SN damage. We report the cases of five patients, each of whom received a large cd of LD over a long period. Fluorodopa positron-emission tomography performed in one case indicated parkinsonism. Autopsies in two cases indicated a normal SN in one and a hypopigmented SN with normal cell complement in the other. Three patients had essential tremor, one had nonprogressive parkinsonism, and one had dopa-responsive dystonia. LD (without decarboxylase inhibitor) was administered over 21 years (cd = 21.99 kg), 9 years (cd = 6.6 kg), 26 years (cd = 18.7 kg), 11 years (cd = 3 kg), and 26 years (cd = 23.93 kg), respectively. None of the patients with essential tremor developed clinical features of parkinsonism that indicated significant SN damage, and one had a normal SN at autopsy. The parkinsonian patient displayed no detectable acceleration of disease process, and the patient with dopa-responsive dystonia had a normal complement of SN neurons at autopsy. We conclude that LD, administered at a dose commonly used for treating Parkinson's disease, was not toxic to SN neurons in these cases.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">9380042</PMID><DateCreated><Year>1997</Year><Month>11</Month><Day>07</Day></DateCreated><DateCompleted><Year>1997</Year><Month>11</Month><Day>07</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>12</Volume><Issue>5</Issue><PubDate><Year>1997</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Is levodopa toxic to human substantia nigra?</ArticleTitle><Pagination><MedlinePgn>634-8</MedlinePgn></Pagination><Abstract><AbstractText>Levodopa (LD) is the most effective drug for symptomatic control of Parkinson's disease, but has been suspected to be toxic to substantia nigra (SN) dopaminergic neurons. Tissue culture and animal studies of LD toxicity have produced contradictory evidence, and one study reported that a human subject exposed to a large cumulative dose (cd) of LD over 4 years had no evidence of SN damage. We report the cases of five patients, each of whom received a large cd of LD over a long period. Fluorodopa positron-emission tomography performed in one case indicated parkinsonism. Autopsies in two cases indicated a normal SN in one and a hypopigmented SN with normal cell complement in the other. Three patients had essential tremor, one had nonprogressive parkinsonism, and one had dopa-responsive dystonia. LD (without decarboxylase inhibitor) was administered over 21 years (cd = 21.99 kg), 9 years (cd = 6.6 kg), 26 years (cd = 18.7 kg), 11 years (cd = 3 kg), and 26 years (cd = 23.93 kg), respectively. None of the patients with essential tremor developed clinical features of parkinsonism that indicated significant SN damage, and one had a normal SN at autopsy. The parkinsonian patient displayed no detectable acceleration of disease process, and the patient with dopa-responsive dystonia had a normal complement of SN neurons at autopsy. We conclude that LD, administered at a dose commonly used for treating Parkinson's disease, was not toxic to SN neurons in these cases.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rajput</LastName><ForeName>A H</ForeName><Initials>AH</Initials><AffiliationInfo><Affiliation>Division of Neurology, Royal University Hospital, Saskatoon, Saskatchewan, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fenton</LastName><ForeName>M e</ForeName><Initials>Me</Initials></Author><Author ValidYN="Y"><LastName>Birdi</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Macaulay</LastName><ForeName>R</ForeName><Initials>R</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</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>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Mov Disord. 1998 Mar;13(2):369-70</RefSource><PMID Version="1">9539360</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000369">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002648">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004421">Dystonia</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007980">Levodopa</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000008">administration & dosage</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000009">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></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></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013378">Substantia Nigra</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName><QualifierName MajorTopicYN="N" UI="Q000503">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013997">Time Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D014055">Tomography, Emission-Computed</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D014202">Tremor</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1997</Year><Month>9</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1997</Year><Month>9</Month><Day>26</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1997</Year><Month>9</Month><Day>26</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9380042</ArticleId><ArticleId IdType="doi">10.1002/mds.870120503</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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