Effect of kynurenine 3‐hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in parkinsonian monkeys
Identifieur interne : 000934 ( Istex/Curation ); précédent : 000933; suivant : 000935Effect of kynurenine 3‐hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in parkinsonian monkeys
Auteurs : Pershia Samadi [Canada] ; Laurent Grégoire [Canada] ; Arash Rassoulpour [États-Unis] ; Paolo Guidetti [États-Unis] ; Emanuela Izzo [Italie] ; Robert Schwarcz [États-Unis] ; Paul J. Bédard [Canada]Source :
- Movement Disorders [ 0885-3185 ] ; 2005-07.
English descriptors
- KwdEn :
Abstract
Homeostatic interactions between dopamine and glutamate are central to the normal physiology of the basal ganglia. This relationship is altered in Parkinsonism and in levodopa‐induced dyskinesias (LID), resulting in an upregulation of corticostriatal glutamatergic function. Kynurenic acid (KYNA), a tryptophan metabolite with antagonist activity at ionotropic glutamate receptors and the capability to inhibit glutamate release presynaptically, might therefore be of therapeutic value in LID. To evaluate this hypothesis, we used a pharmacological tool, the kynurenine 3‐hydroxylase inhibitor Ro 61‐8048, which raises KYNA levels acutely. Ro 61‐8048 was tested in MPTP cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias after each dose of levodopa. Serum and CSF concentrations of KYNA and its precursor kynurenine increased dose‐dependently after Ro 61‐8048 administration, alone or in combination with levodopa. Coadministration of Ro 61‐8048 with levodopa produced a moderate but significant reduction in the severity of dyskinesias while maintaining the motor benefit. These results suggest that elevation of KYNA levels through inhibition of kynurenine 3‐hydroxylase constitutes a promising novel approach for managing LID in Parkinson's disease. © 2005 Movement Disorder Society
Url:
DOI: 10.1002/mds.20596
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000934
Links to Exploration step
ISTEX:256B7C33FBCE6776065D822ED459000FF7F568DALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of kynurenine 3‐hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in parkinsonian monkeys</title><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><mods:affiliation>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Département de Medicine, Université Laval, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Medicine, Université Laval, Québec</wicri:regionArea></affiliation></author><author><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Grégoire">Laurent Grégoire</name><affiliation wicri:level="1"><mods:affiliation>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec</wicri:regionArea></affiliation></author><author><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name><affiliation wicri:level="1"><mods:affiliation>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name><affiliation wicri:level="1"><mods:affiliation>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name><affiliation wicri:level="1"><mods:affiliation>Newron Pharmaceuticals, Bresso, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Newron Pharmaceuticals, Bresso</wicri:regionArea></affiliation></author><author><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name><affiliation wicri:level="1"><mods:affiliation>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bédard">Paul J. Bédard</name><affiliation wicri:level="1"><mods:affiliation>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Département de Medicine, Université Laval, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Medicine, Université Laval, Québec</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:256B7C33FBCE6776065D822ED459000FF7F568DA</idno><date when="2005" year="2005">2005</date><idno type="doi">10.1002/mds.20596</idno><idno type="url">https://api.istex.fr/document/256B7C33FBCE6776065D822ED459000FF7F568DA/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000934</idno><idno type="wicri:Area/Istex/Curation">000934</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Effect of kynurenine 3‐hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in parkinsonian monkeys</title><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><mods:affiliation>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Département de Medicine, Université Laval, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Medicine, Université Laval, Québec</wicri:regionArea></affiliation></author><author><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Grégoire">Laurent Grégoire</name><affiliation wicri:level="1"><mods:affiliation>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec</wicri:regionArea></affiliation></author><author><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name><affiliation wicri:level="1"><mods:affiliation>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name><affiliation wicri:level="1"><mods:affiliation>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name><affiliation wicri:level="1"><mods:affiliation>Newron Pharmaceuticals, Bresso, Italy</mods:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Newron Pharmaceuticals, Bresso</wicri:regionArea></affiliation></author><author><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name><affiliation wicri:level="1"><mods:affiliation>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bédard">Paul J. Bédard</name><affiliation wicri:level="1"><mods:affiliation>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de Recherche en Neurosciences, Centre Hospitalier Universitaire de Québec, Québec</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Département de Medicine, Université Laval, Québec, Canada</mods:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Medicine, Université Laval, Québec</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2005-07">2005-07</date><biblScope unit="vol">20</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="792">792</biblScope><biblScope unit="page" to="802">802</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">256B7C33FBCE6776065D822ED459000FF7F568DA</idno><idno type="DOI">10.1002/mds.20596</idno><idno type="ArticleID">MDS20596</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>MPTP</term><term>Parkinson's disease</term><term>dyskinesia</term><term>glutamate</term><term>kynurenic acid</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Homeostatic interactions between dopamine and glutamate are central to the normal physiology of the basal ganglia. This relationship is altered in Parkinsonism and in levodopa‐induced dyskinesias (LID), resulting in an upregulation of corticostriatal glutamatergic function. Kynurenic acid (KYNA), a tryptophan metabolite with antagonist activity at ionotropic glutamate receptors and the capability to inhibit glutamate release presynaptically, might therefore be of therapeutic value in LID. To evaluate this hypothesis, we used a pharmacological tool, the kynurenine 3‐hydroxylase inhibitor Ro 61‐8048, which raises KYNA levels acutely. Ro 61‐8048 was tested in MPTP cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias after each dose of levodopa. Serum and CSF concentrations of KYNA and its precursor kynurenine increased dose‐dependently after Ro 61‐8048 administration, alone or in combination with levodopa. Coadministration of Ro 61‐8048 with levodopa produced a moderate but significant reduction in the severity of dyskinesias while maintaining the motor benefit. These results suggest that elevation of KYNA levels through inhibition of kynurenine 3‐hydroxylase constitutes a promising novel approach for managing LID in Parkinson's disease. © 2005 Movement Disorder Society</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000934 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 000934 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= MovDisordV3
|flux= Istex
|étape= Curation
|type= RBID
|clé= ISTEX:256B7C33FBCE6776065D822ED459000FF7F568DA
|texte= Effect of kynurenine 3‐hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in parkinsonian monkeys
}}
| This area was generated with Dilib version V0.6.23. |  |