Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys
Identifieur interne : 002366 ( Main/Exploration ); précédent : 002365; suivant : 002367Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys
Auteurs : Laurent Gregoire [Canada] ; Arash Rassoulpour [États-Unis] ; Paolo Guidetti [États-Unis] ; Pershia Samadi [Canada] ; Paul J. Bedard [Canada] ; Emanuela Izzo [Italie] ; Robert Schwarcz [États-Unis] ; Therese Di Paolo [Canada]Source :
- Behavioural brain research [ 0166-4328 ] ; 2008.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Increased glutamatergic activity is believed to play a significant role in the development of levodopa-induced dyskinesias (LID). LID may therefore be attenuated by a reduction in glutamatergic function. This was tested pharmacologically in MPTP monkeys by increasing the formation of kynurenic acid (KYNA), a tryptophan metabolite that inhibits glutamate release and also blocks NMDA receptors directly. KYNA synthesis was stimulated by prolonged systemic administration of the kynurenine 3-hydroxylase inhibitor Ro 61-8048. Four MPTP cynomolgus monkeys received L-dopa (LD; 100 mg) with benserazide (25 mg) for one month. Progressively, all these animals developed LID. Four other MPTP monkeys received Ro 61-8048 (50 mg/kg) daily 3 h before administration of LD/benserazide for one month. The addition of Ro 61-8048 reduced the development of LID but did not affect the antiparkinsonian efficacy of LD. Moreover, Ro 61-8048 administration caused sustained increases in serum kynurenine and KYNA concentrations, which reverted to basal values 24 h after the last treatment. This effect of Ro 61-8048 was less pronounced in the CSF. These results demonstrate that long-lasting elevation of KYNA levels caused by prolonged inhibition of kynurenine 3-hydroxylase is associated with a significant reduction in LID but does not compromise the benefits of chronic LD therapy.
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 000684
- to stream PascalFrancis, to step Corpus: 000697
- to stream PascalFrancis, to step Curation: 000626
- to stream PascalFrancis, to step Checkpoint: 000500
- to stream Main, to step Merge: 002561
- to stream Main, to step Curation: 002366
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="fr" level="a">Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys</title><author><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Gregoire">Laurent Gregoire</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University</s1><s2>Québec, PQ</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, PQ</wicri:noRegion></affiliation></author><author><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Maryland Psychiatric Research Center, University of Maryland School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Baltimore, MD</wicri:noRegion></affiliation></author><author><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Maryland Psychiatric Research Center, University of Maryland School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Baltimore, MD</wicri:noRegion></affiliation></author><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University</s1><s2>Québec, PQ</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, PQ</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, CHUQ, CHUL Pavillon and Faculty of Medicine, Laval University</s1><s2>Quebec, PQ</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, PQ</wicri:noRegion></affiliation></author><author><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Newron Pharmaceuticals</s1><s2>Bresso</s2><s3>ITA</s3><sZ>6 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Newron Pharmaceuticals</wicri:noRegion></affiliation></author><author><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Maryland Psychiatric Research Center, University of Maryland School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Baltimore, MD</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University</s1><s2>Québec, PQ</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, PQ</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">08-0025718</idno><date when="2008">2008</date><idno type="stanalyst">PASCAL 08-0025718 INIST</idno><idno type="RBID">Pascal:08-0025718</idno><idno type="wicri:Area/PascalFrancis/Corpus">000684</idno><idno type="stanalyst">FRANCIS 08-0025718 INIST</idno><idno type="wicri:Area/PascalFrancis/Corpus">000697</idno><idno type="wicri:Area/PascalFrancis/Curation">000626</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000500</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000500</idno><idno type="wicri:doubleKey">0166-4328:2008:Gregoire L:prolonged:kynurenine:hydroxylase</idno><idno type="wicri:Area/Main/Merge">002561</idno><idno type="wicri:Area/Main/Curation">002366</idno><idno type="wicri:Area/Main/Exploration">002366</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="fr" level="a">Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys</title><author><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Gregoire">Laurent Gregoire</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University</s1><s2>Québec, PQ</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, PQ</wicri:noRegion></affiliation></author><author><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Maryland Psychiatric Research Center, University of Maryland School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Baltimore, MD</wicri:noRegion></affiliation></author><author><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Maryland Psychiatric Research Center, University of Maryland School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Baltimore, MD</wicri:noRegion></affiliation></author><author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University</s1><s2>Québec, PQ</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, PQ</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research Unit, CHUQ, CHUL Pavillon and Faculty of Medicine, Laval University</s1><s2>Quebec, PQ</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec, PQ</wicri:noRegion></affiliation></author><author><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Newron Pharmaceuticals</s1><s2>Bresso</s2><s3>ITA</s3><sZ>6 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Newron Pharmaceuticals</wicri:noRegion></affiliation></author><author><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Maryland Psychiatric Research Center, University of Maryland School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Baltimore, MD</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University</s1><s2>Québec, PQ</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, PQ</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Behavioural brain research</title><title level="j" type="abbreviated">Behav. brain res.</title><idno type="ISSN">0166-4328</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Behavioural brain research</title><title level="j" type="abbreviated">Behav. brain res.</title><idno type="ISSN">0166-4328</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiparkinson agent</term><term>Dyskinesia</term><term>Inhibition</term><term>Kynurenic acid</term><term>Kynurenine</term><term>Levodopa</term><term>Motor control</term><term>Neurotoxin</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Cynurénine</term><term>Inhibition</term><term>Lévodopa</term><term>Dyskinésie</term><term>Neurotoxine</term><term>Maladie de Parkinson</term><term>Antiparkinsonien</term><term>Contrôle moteur</term><term>MPTP</term><term>Cynurénique acide</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Increased glutamatergic activity is believed to play a significant role in the development of levodopa-induced dyskinesias (LID). LID may therefore be attenuated by a reduction in glutamatergic function. This was tested pharmacologically in MPTP monkeys by increasing the formation of kynurenic acid (KYNA), a tryptophan metabolite that inhibits glutamate release and also blocks NMDA receptors directly. KYNA synthesis was stimulated by prolonged systemic administration of the kynurenine 3-hydroxylase inhibitor Ro 61-8048. Four MPTP cynomolgus monkeys received L-dopa (LD; 100 mg) with benserazide (25 mg) for one month. Progressively, all these animals developed LID. Four other MPTP monkeys received Ro 61-8048 (50 mg/kg) daily 3 h before administration of LD/benserazide for one month. The addition of Ro 61-8048 reduced the development of LID but did not affect the antiparkinsonian efficacy of LD. Moreover, Ro 61-8048 administration caused sustained increases in serum kynurenine and KYNA concentrations, which reverted to basal values 24 h after the last treatment. This effect of Ro 61-8048 was less pronounced in the CSF. These results demonstrate that long-lasting elevation of KYNA levels caused by prolonged inhibition of kynurenine 3-hydroxylase is associated with a significant reduction in LID but does not compromise the benefits of chronic LD therapy.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Italie</li><li>États-Unis</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Gregoire">Laurent Gregoire</name></noRegion><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name></country><country name="États-Unis"><noRegion><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name></noRegion><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name></country><country name="Italie"><noRegion><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002366 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002366 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= Pascal:08-0025718
|texte= Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys
}}
| This area was generated with Dilib version V0.6.29. |  |