ParkinsonCanadaV1, PascalFrancis, Corpus, bibRecord, 000697

Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys

Identifieur interne : 000697 ( PascalFrancis/Corpus ); précédent : 000696; suivant : 000698

Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys

Auteurs : Laurent Gregoire ; Arash Rassoulpour ; Paolo Guidetti ; Pershia Samadi ; Paul J. Bedard ; Emanuela Izzo ; Robert Schwarcz ; Therese Di Paolo

Source :

Behavioural brain research [ 0166-4328 ] ; 2008.

RBID : Francis:08-0025718

Descripteurs français

Pascal (Inist)
- Cynurénine, Inhibition, Lévodopa, Dyskinésie, Neurotoxine, Maladie de Parkinson, Antiparkinsonien, Contrôle moteur, MPTP, Cynurénique acide.

English descriptors

KwdEn :
- Antiparkinson agent, Dyskinesia, Inhibition, Kynurenic acid, Kynurenine, Levodopa, Motor control, Neurotoxin, Parkinson disease.

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.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

A01	`01`	`1`		`@0 0166-4328`
A02	`01`			`@0 BBREDI`
A03		`1`		`@0 Behav. brain res.`
A05				`@2 186`
A06				`@2 2`
A08	`01`	`1`	`FRE`	`@1 Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys`
A11	`01`	`1`		`@1 GREGOIRE (Laurent)`
A11	`02`	`1`		`@1 RASSOULPOUR (Arash)`
A11	`03`	`1`		`@1 GUIDETTI (Paolo)`
A11	`04`	`1`		`@1 SAMADI (Pershia)`
A11	`05`	`1`		`@1 BEDARD (Paul J.)`
A11	`06`	`1`		`@1 IZZO (Emanuela)`
A11	`07`	`1`		`@1 SCHWARCZ (Robert)`
A11	`08`	`1`		`@1 DI PAOLO (Therese)`
A14	`01`			`@1 Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University @2 Québec, PQ @3 CAN @Z 1 aut. @Z 4 aut. @Z 8 aut.`
A14	`02`			`@1 Maryland Psychiatric Research Center, University of Maryland School of Medicine @2 Baltimore, MD @3 USA @Z 2 aut. @Z 3 aut. @Z 7 aut.`
A14	`03`			`@1 Neuroscience Research Unit, CHUQ, CHUL Pavillon and Faculty of Medicine, Laval University @2 Quebec, PQ @3 CAN @Z 5 aut.`
A14	`04`			`@1 Newron Pharmaceuticals @2 Bresso @3 ITA @Z 6 aut.`
A20				`@1 161-167`
A21				`@1 2008`
A23	`01`			`@0 FRE`
A24	`01`			`@0 eng`
A43	`01`			`@1 INIST @2 18271 @5 354000174302090020`
A44				`@0 0000 @1 © 2008 INIST-CNRS. All rights reserved.`
A45				`@0 50 ref.`
A47	`01`	`1`		`@0 08-0025718`
A60				`@1 P`
A61				`@0 A`
A64	`01`	`1`		`@0 Behavioural brain research`
A66	`01`			`@0 IRL`
C01	`01`		`ENG`	@0 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.
C02	`01`	`X`		`@0 770B03 @1 II`
C03	`01`	`X`	`FRE`	`@0 Cynurénine @5 01`
C03	`01`	`X`	`ENG`	`@0 Kynurenine @5 01`
C03	`01`	`X`	`SPA`	`@0 Cinurenina @5 01`
C03	`02`	`X`	`FRE`	`@0 Inhibition @5 02`
C03	`02`	`X`	`ENG`	`@0 Inhibition @5 02`
C03	`02`	`X`	`SPA`	`@0 Inhibición @5 02`
C03	`03`	`X`	`FRE`	`@0 Lévodopa @2 NK @2 FR @5 03`
C03	`03`	`X`	`ENG`	`@0 Levodopa @2 NK @2 FR @5 03`
C03	`03`	`X`	`SPA`	`@0 Levodopa @2 NK @2 FR @5 03`
C03	`04`	`X`	`FRE`	`@0 Dyskinésie @5 04`
C03	`04`	`X`	`ENG`	`@0 Dyskinesia @5 04`
C03	`04`	`X`	`SPA`	`@0 Disquinesia @5 04`
C03	`05`	`X`	`FRE`	`@0 Neurotoxine @5 05`
C03	`05`	`X`	`ENG`	`@0 Neurotoxin @5 05`
C03	`05`	`X`	`SPA`	`@0 Neurotoxina @5 05`
C03	`06`	`X`	`FRE`	`@0 Maladie de Parkinson @2 NM @5 06`
C03	`06`	`X`	`ENG`	`@0 Parkinson disease @2 NM @5 06`
C03	`06`	`X`	`SPA`	`@0 Parkinson enfermedad @2 NM @5 06`
C03	`07`	`X`	`FRE`	`@0 Antiparkinsonien @5 31`
C03	`07`	`X`	`ENG`	`@0 Antiparkinson agent @5 31`
C03	`07`	`X`	`SPA`	`@0 Antiparkinsoniano @5 31`
C03	`08`	`X`	`FRE`	`@0 Contrôle moteur @5 32`
C03	`08`	`X`	`ENG`	`@0 Motor control @5 32`
C03	`08`	`X`	`SPA`	`@0 Control motor @5 32`
C03	`09`	`X`	`FRE`	`@0 MPTP @4 INC @5 86`
C03	`10`	`X`	`FRE`	`@0 Cynurénique acide @4 CD @5 96`
C03	`10`	`X`	`ENG`	`@0 Kynurenic acid @4 CD @5 96`
C07	`01`	`X`	`FRE`	`@0 Toxine`
C07	`01`	`X`	`ENG`	`@0 Toxin`
C07	`01`	`X`	`SPA`	`@0 Toxina`
C07	`02`	`X`	`FRE`	`@0 Agoniste @5 37`
C07	`02`	`X`	`ENG`	`@0 Agonist @5 37`
C07	`02`	`X`	`SPA`	`@0 Agonista @5 37`
C07	`03`	`X`	`FRE`	`@0 Récepteur dopaminergique D2 @5 38`
C07	`03`	`X`	`ENG`	`@0 D2 Dopamine receptor @5 38`
C07	`03`	`X`	`SPA`	`@0 Receptor dopaminérgico D2 @5 38`
C07	`04`	`X`	`FRE`	`@0 Syndrome extrapyramidal @5 39`
C07	`04`	`X`	`ENG`	`@0 Extrapyramidal syndrome @5 39`
C07	`04`	`X`	`SPA`	`@0 Extrapiramidal síndrome @5 39`
C07	`05`	`X`	`FRE`	`@0 Mouvement involontaire @5 40`
C07	`05`	`X`	`ENG`	`@0 Involuntary movement @5 40`
C07	`05`	`X`	`SPA`	`@0 Movimiento involuntario @5 40`
C07	`06`	`X`	`FRE`	`@0 Pathologie du système nerveux @5 41`
C07	`06`	`X`	`ENG`	`@0 Nervous system diseases @5 41`
C07	`06`	`X`	`SPA`	`@0 Sistema nervioso patología @5 41`
C07	`07`	`X`	`FRE`	`@0 Trouble neurologique @5 42`
C07	`07`	`X`	`ENG`	`@0 Neurological disorder @5 42`
C07	`07`	`X`	`SPA`	`@0 Trastorno neurológico @5 42`
C07	`08`	`X`	`FRE`	`@0 Pathologie de l'encéphale @5 43`
C07	`08`	`X`	`ENG`	`@0 Cerebral disorder @5 43`
C07	`08`	`X`	`SPA`	`@0 Encéfalo patología @5 43`
C07	`09`	`X`	`FRE`	`@0 Maladie dégénérative @5 44`
C07	`09`	`X`	`ENG`	`@0 Degenerative disease @5 44`
C07	`09`	`X`	`SPA`	`@0 Enfermedad degenerativa @5 44`
C07	`10`	`X`	`FRE`	`@0 Pathologie du système nerveux central @5 45`
C07	`10`	`X`	`ENG`	`@0 Central nervous system disease @5 45`
C07	`10`	`X`	`SPA`	`@0 Sistema nervosio central patología @5 45`
N21				`@1 009`
N44	`01`			`@1 OTO`
N82				`@1 OTO`

Format Inist (serveur)

NO :	FRANCIS 08-0025718 INIST
FT :	Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys
AU :	GREGOIRE (Laurent); RASSOULPOUR (Arash); GUIDETTI (Paolo); SAMADI (Pershia); BEDARD (Paul J.); IZZO (Emanuela); SCHWARCZ (Robert); DI PAOLO (Therese)
AF :	Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University/Québec, PQ/Canada (1 aut., 4 aut., 8 aut.); Maryland Psychiatric Research Center, University of Maryland School of Medicine/Baltimore, MD/Etats-Unis (2 aut., 3 aut., 7 aut.); Neuroscience Research Unit, CHUQ, CHUL Pavillon and Faculty of Medicine, Laval University/Quebec, PQ/Canada (5 aut.); Newron Pharmaceuticals/Bresso/Italie (6 aut.)
DT :	Publication en série; Niveau analytique
SO :	Behavioural brain research; ISSN 0166-4328; Coden BBREDI; Irlande; Da. 2008; Vol. 186; No. 2; Pp. 161-167; Abs. anglais; Bibl. 50 ref.
LA :	Français
EA :	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.
CC :	770B03
FD :	Cynurénine; Inhibition; Lévodopa; Dyskinésie; Neurotoxine; Maladie de Parkinson; Antiparkinsonien; Contrôle moteur; MPTP; Cynurénique acide
FG :	Toxine; Agoniste; Récepteur dopaminergique D2; Syndrome extrapyramidal; Mouvement involontaire; Pathologie du système nerveux; Trouble neurologique; Pathologie de l'encéphale; Maladie dégénérative; Pathologie du système nerveux central
ED :	Kynurenine; Inhibition; Levodopa; Dyskinesia; Neurotoxin; Parkinson disease; Antiparkinson agent; Motor control; Kynurenic acid
EG :	Toxin; Agonist; D2 Dopamine receptor; Extrapyramidal syndrome; Involuntary movement; Nervous system diseases; Neurological disorder; Cerebral disorder; Degenerative disease; Central nervous system disease
SD :	Cinurenina; Inhibición; Levodopa; Disquinesia; Neurotoxina; Parkinson enfermedad; Antiparkinsoniano; Control motor
LO :	INIST-18271.354000174302090020
ID :	08-0025718

Links to Exploration step

Francis:08-0025718

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><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>
</affiliation>
</author>
<author><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name>
<affiliation><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>
</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><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>
</affiliation>
</author>
<author><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name>
<affiliation><inist:fA14 i1="04"><s1>Newron Pharmaceuticals</s1>
<s2>Bresso</s2>
<s3>ITA</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name>
<affiliation><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>
</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><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>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">08-0025718</idno>
<date when="2008">2008</date>
<idno type="stanalyst">FRANCIS 08-0025718 INIST</idno>
<idno type="RBID">Francis:08-0025718</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000697</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><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>
</affiliation>
</author>
<author><name sortKey="Rassoulpour, Arash" sort="Rassoulpour, Arash" uniqKey="Rassoulpour A" first="Arash" last="Rassoulpour">Arash Rassoulpour</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Guidetti, Paolo" sort="Guidetti, Paolo" uniqKey="Guidetti P" first="Paolo" last="Guidetti">Paolo Guidetti</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Samadi, Pershia" sort="Samadi, Pershia" uniqKey="Samadi P" first="Pershia" last="Samadi">Pershia Samadi</name>
<affiliation><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>
</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><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>
</affiliation>
</author>
<author><name sortKey="Izzo, Emanuela" sort="Izzo, Emanuela" uniqKey="Izzo E" first="Emanuela" last="Izzo">Emanuela Izzo</name>
<affiliation><inist:fA14 i1="04"><s1>Newron Pharmaceuticals</s1>
<s2>Bresso</s2>
<s3>ITA</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Schwarcz, Robert" sort="Schwarcz, Robert" uniqKey="Schwarcz R" first="Robert" last="Schwarcz">Robert Schwarcz</name>
<affiliation><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>
</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><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>
</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>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0166-4328</s0>
</fA01>
<fA02 i1="01"><s0>BBREDI</s0>
</fA02>
<fA03 i2="1"><s0>Behav. brain res.</s0>
</fA03>
<fA05><s2>186</s2>
</fA05>
<fA06><s2>2</s2>
</fA06>
<fA08 i1="01" i2="1" l="FRE"><s1>Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>GREGOIRE (Laurent)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>RASSOULPOUR (Arash)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>GUIDETTI (Paolo)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>SAMADI (Pershia)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>BEDARD (Paul J.)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>IZZO (Emanuela)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>SCHWARCZ (Robert)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>DI PAOLO (Therese)</s1>
</fA11>
<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>
</fA14>
<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>
</fA14>
<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>
</fA14>
<fA14 i1="04"><s1>Newron Pharmaceuticals</s1>
<s2>Bresso</s2>
<s3>ITA</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA20><s1>161-167</s1>
</fA20>
<fA21><s1>2008</s1>
</fA21>
<fA23 i1="01"><s0>FRE</s0>
</fA23>
<fA24 i1="01"><s0>eng</s0>
</fA24>
<fA43 i1="01"><s1>INIST</s1>
<s2>18271</s2>
<s5>354000174302090020</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2008 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>50 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>08-0025718</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Behavioural brain research</s0>
</fA64>
<fA66 i1="01"><s0>IRL</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>770B03</s0>
<s1>II</s1>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Cynurénine</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Kynurenine</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Cinurenina</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Inhibition</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Inhibition</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Inhibición</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Lévodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Dyskinésie</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Dyskinesia</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Disquinesia</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Neurotoxine</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Neurotoxin</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Neurotoxina</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Maladie de Parkinson</s0>
<s2>NM</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Parkinson disease</s0>
<s2>NM</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Parkinson enfermedad</s0>
<s2>NM</s2>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Antiparkinsonien</s0>
<s5>31</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Antiparkinson agent</s0>
<s5>31</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Antiparkinsoniano</s0>
<s5>31</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Contrôle moteur</s0>
<s5>32</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Motor control</s0>
<s5>32</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Control motor</s0>
<s5>32</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>MPTP</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Cynurénique acide</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Kynurenic acid</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Toxine</s0>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Toxin</s0>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Toxina</s0>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Agoniste</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Agonist</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Agonista</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Récepteur dopaminergique D2</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>D2 Dopamine receptor</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Receptor dopaminérgico D2</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Mouvement involontaire</s0>
<s5>40</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Involuntary movement</s0>
<s5>40</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Movimiento involuntario</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Pathologie du   système nerveux</s0>
<s5>41</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Nervous system diseases</s0>
<s5>41</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Sistema nervioso patología</s0>
<s5>41</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Trouble neurologique</s0>
<s5>42</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Neurological disorder</s0>
<s5>42</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Trastorno neurológico</s0>
<s5>42</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0>
<s5>43</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Cerebral disorder</s0>
<s5>43</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Encéfalo patología</s0>
<s5>43</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Maladie dégénérative</s0>
<s5>44</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Degenerative disease</s0>
<s5>44</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0>
<s5>44</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Pathologie du   système nerveux central</s0>
<s5>45</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Central nervous system disease</s0>
<s5>45</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0>
<s5>45</s5>
</fC07>
<fN21><s1>009</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
<server><NO>FRANCIS 08-0025718 INIST</NO>
<FT>Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys</FT>
<AU>GREGOIRE (Laurent); RASSOULPOUR (Arash); GUIDETTI (Paolo); SAMADI (Pershia); BEDARD (Paul J.); IZZO (Emanuela); SCHWARCZ (Robert); DI PAOLO (Therese)</AU>
<AF>Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavilion and Faculty of Pharmacy, Laval University/Québec, PQ/Canada (1 aut., 4 aut., 8 aut.); Maryland Psychiatric Research Center, University of Maryland School of Medicine/Baltimore, MD/Etats-Unis (2 aut., 3 aut., 7 aut.); Neuroscience Research Unit, CHUQ, CHUL Pavillon and Faculty of Medicine, Laval University/Quebec, PQ/Canada (5 aut.); Newron Pharmaceuticals/Bresso/Italie (6 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Behavioural brain research; ISSN 0166-4328; Coden BBREDI; Irlande; Da. 2008; Vol. 186; No. 2; Pp. 161-167; Abs. anglais; Bibl. 50 ref.</SO>
<LA>Français</LA>
<EA>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.</EA>
<CC>770B03</CC>
<FD>Cynurénine; Inhibition; Lévodopa; Dyskinésie; Neurotoxine; Maladie de Parkinson; Antiparkinsonien; Contrôle moteur; MPTP; Cynurénique acide</FD>
<FG>Toxine; Agoniste; Récepteur dopaminergique D2; Syndrome extrapyramidal; Mouvement involontaire; Pathologie du   système nerveux; Trouble neurologique; Pathologie de l'encéphale; Maladie dégénérative; Pathologie du système nerveux central</FG>
<ED>Kynurenine; Inhibition; Levodopa; Dyskinesia; Neurotoxin; Parkinson disease; Antiparkinson agent; Motor control; Kynurenic acid</ED>
<EG>Toxin; Agonist; D2 Dopamine receptor; Extrapyramidal syndrome; Involuntary movement; Nervous system diseases; Neurological disorder; Cerebral disorder; Degenerative disease; Central nervous system disease</EG>
<SD>Cinurenina; Inhibición; Levodopa; Disquinesia; Neurotoxina; Parkinson enfermedad; Antiparkinsoniano; Control motor</SD>
<LO>INIST-18271.354000174302090020</LO>
<ID>08-0025718</ID>
</server>
</inist>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/PascalFrancis/Corpus

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000697 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Corpus/biblio.hfd -nk 000697 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
   |flux=    PascalFrancis
   |étape=   Corpus
   |type=    RBID
   |clé=     Francis: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.
Data generation: Thu May 4 22:20:19 2017. Site generation: Fri Dec 23 23:17:26 2022

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

La maladie de Parkinson au Canada (serveur d'exploration)

Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys

Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys

Source :

Descripteurs français

English descriptors

Abstract

Notice en format standard (ISO 2709)

Format Inist (serveur)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri