L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.
Identifieur interne : 000921 ( PubMed/Corpus ); précédent : 000920; suivant : 000922L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.
Auteurs : Sylvia Navailles ; Manolo Carta ; Martin Guthrie ; Philippe De DeurwaerdèreSource :
- Central nervous system agents in medicinal chemistry [ 1875-6166 ] ; 2011.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (metabolism), Antiparkinson Agents (pharmacology), Antiparkinson Agents (therapeutic use), Dopamine (metabolism), Humans, Levodopa (metabolism), Levodopa (pharmacology), Levodopa (therapeutic use), Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Serotonergic Neurons (drug effects), Serotonergic Neurons (metabolism), Serotonin (metabolism).
- MESH :
- chemical , metabolism : Antiparkinson Agents, Dopamine, Levodopa, Serotonin.
- chemical , pharmacology : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- drug effects : Serotonergic Neurons.
- drug therapy : Parkinson Disease.
- metabolism : Parkinson Disease, Serotonergic Neurons.
- Animals, Humans.
Abstract
L-DOPA is the gold standard medication of Parkinson's disease, a neurological disorder consequent upon the degeneration of mesencephalic dopaminergic neurons. The therapeutic efficacy of L-DOPA has been related to its ability to restore dopamine (DA) extracellular levels in the Parkinsonian brain. The origin of the L-DOPA-induced rise in DA has been the object of numerous studies and controversies but the data collectively point to serotonergic (5-HT) neurons as being most significant in the release. Here, we review biochemical and behavioral evidence supporting serotonergic neurons as playing the main role in the actions of L-DOPA, considered from two points of view. The main aspect concerns the biochemical demonstration that 5-HT neurons are almost solely implicated in the release of DA induced by L-DOPA. The mechanism of action of L-DOPA inside 5-HT neurons will be thoroughly dissected on the basis of L-DOPA effects on extracellular versus tissue DA levels. The unique contribution of 5-HT neurons in mediating the release of newly synthesised DA from L-DOPA will be discussed in parallel with DA-dependent behaviors induced by L-DOPA. The other, and neglected, aspect concerns the possible deleterious impact of the presence of L-DOPA inside 5-HT neurons on 5-HT neuronal function. Overall, the fact that 5-HT neurons release the newly synthesised DA from L-DOPA in multiple brain regions beyond the striatum gives new insight into the large impact of L-DOPA in the Parkinsonian brain and strengthens therapeutic perspectives targeting the 5-HT system to reduce both motor and non-motor complications of L-DOPA medication.
PubMed: 22117594
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pubmed:22117594Le document en format XML
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The therapeutic efficacy of L-DOPA has been related to its ability to restore dopamine (DA) extracellular levels in the Parkinsonian brain. The origin of the L-DOPA-induced rise in DA has been the object of numerous studies and controversies but the data collectively point to serotonergic (5-HT) neurons as being most significant in the release. Here, we review biochemical and behavioral evidence supporting serotonergic neurons as playing the main role in the actions of L-DOPA, considered from two points of view. The main aspect concerns the biochemical demonstration that 5-HT neurons are almost solely implicated in the release of DA induced by L-DOPA. The mechanism of action of L-DOPA inside 5-HT neurons will be thoroughly dissected on the basis of L-DOPA effects on extracellular versus tissue DA levels. The unique contribution of 5-HT neurons in mediating the release of newly synthesised DA from L-DOPA will be discussed in parallel with DA-dependent behaviors induced by L-DOPA. The other, and neglected, aspect concerns the possible deleterious impact of the presence of L-DOPA inside 5-HT neurons on 5-HT neuronal function. Overall, the fact that 5-HT neurons release the newly synthesised DA from L-DOPA in multiple brain regions beyond the striatum gives new insight into the large impact of L-DOPA in the Parkinsonian brain and strengthens therapeutic perspectives targeting the 5-HT system to reduce both motor and non-motor complications of L-DOPA medication.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22117594</PMID><DateCreated><Year>2012</Year><Month>03</Month><Day>05</Day></DateCreated><DateCompleted><Year>2012</Year><Month>11</Month><Day>08</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1875-6166</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>4</Issue><PubDate><Year>2011</Year><Month>Dec</Month><Day>01</Day></PubDate></JournalIssue><Title>Central nervous system agents in medicinal chemistry</Title><ISOAbbreviation>Cent Nerv Syst Agents Med Chem</ISOAbbreviation></Journal><ArticleTitle>L-DOPA and serotonergic neurons: functional implication and therapeutic perspectives in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>305-20</MedlinePgn></Pagination><Abstract><AbstractText>L-DOPA is the gold standard medication of Parkinson's disease, a neurological disorder consequent upon the degeneration of mesencephalic dopaminergic neurons. The therapeutic efficacy of L-DOPA has been related to its ability to restore dopamine (DA) extracellular levels in the Parkinsonian brain. The origin of the L-DOPA-induced rise in DA has been the object of numerous studies and controversies but the data collectively point to serotonergic (5-HT) neurons as being most significant in the release. Here, we review biochemical and behavioral evidence supporting serotonergic neurons as playing the main role in the actions of L-DOPA, considered from two points of view. The main aspect concerns the biochemical demonstration that 5-HT neurons are almost solely implicated in the release of DA induced by L-DOPA. The mechanism of action of L-DOPA inside 5-HT neurons will be thoroughly dissected on the basis of L-DOPA effects on extracellular versus tissue DA levels. The unique contribution of 5-HT neurons in mediating the release of newly synthesised DA from L-DOPA will be discussed in parallel with DA-dependent behaviors induced by L-DOPA. The other, and neglected, aspect concerns the possible deleterious impact of the presence of L-DOPA inside 5-HT neurons on 5-HT neuronal function. Overall, the fact that 5-HT neurons release the newly synthesised DA from L-DOPA in multiple brain regions beyond the striatum gives new insight into the large impact of L-DOPA in the Parkinsonian brain and strengthens therapeutic perspectives targeting the 5-HT system to reduce both motor and non-motor complications of L-DOPA medication.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Navailles</LastName><ForeName>Sylvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Université de Bordeaux, Unité Mixte de Recherche Centre National de la Recherche Scientifique 5293, 33076 Bordeaux cedex, France. sylvia.navailles@u-bordeaux2.fr</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carta</LastName><ForeName>Manolo</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Guthrie</LastName><ForeName>Martin</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>De Deurwaerdère</LastName><ForeName>Philippe</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Cent Nerv Syst Agents Med Chem</MedlineTA><NlmUniqueID>101269163</NlmUniqueID><ISSNLinking>1871-5249</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>333DO1RDJY</RegistryNumber><NameOfSubstance UI="D012701">Serotonin</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber><NameOfSubstance UI="D004298">Dopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000978" MajorTopicYN="N">Antiparkinson Agents</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004298" MajorTopicYN="N">Dopamine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059326" MajorTopicYN="N">Serotonergic Neurons</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012701" MajorTopicYN="N">Serotonin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2011</Year><Month>09</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2011</Year><Month>10</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2011</Year><Month>10</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>11</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>11</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>11</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22117594</ArticleId><ArticleId IdType="pii">BSP/CNSAMC/E-Pub/# 46</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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