ParkinsonFranceV1, PascalFrancis, Curation, bibRecord, 000613

Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole

Identifieur interne : 000613 ( PascalFrancis/Curation ); précédent : 000612; suivant : 000614

Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole

Auteurs : Jeffrey N. Joyce [États-Unis] ; Steve Presgraves [États-Unis] ; Lynn Renish [États-Unis] ; Sabinne Borwege [États-Unis] ; Tracy Osredkar [États-Unis] ; Diane Hagner [États-Unis] ; Maria Replogle [États-Unis] ; Mateo Pazsoldan [États-Unis] ; Mark J. Millan [France]

Source :

Experimental neurology : (Print) [ 0014-4886 ] ; 2003.

RBID : Pascal:04-0276961

Descripteurs français

Pascal (Inist)
- Parkinson maladie, Récepteur dopaminergique D3, Récepteur dopaminergique D2, Système nerveux pathologie, Antiparkinsonien, In vitro, Etude comparative, Ropinirole, Dérivée, Animal, Primates, Modèle, Pramipexole, Mort cellulaire, Subchronique, Traitement, Souris, Tyrosine 3-monooxygenase, Locus niger, Aire tegmentaire ventrale, Dose forte.

English descriptors

KwdEn :
- Animal, Antiparkinson agent, Cell death, Comparative study, D2 Dopamine receptor, D3 Dopamine receptor, Derivative, High dose, In vitro, Locus niger, Models, Mouse, Nervous system diseases, Parkinson disease, Pramipexole, Primates, Ropinirole, Subchronic, Treatment, Tyrosine 3-monooxygenase, Ventral tegmental area.

Abstract

The novel naphtoxazine derivative and preferential D, vs D₂ receptor agonist, S32504, restores perturbed motor function in rodent and primate models of antiparkinsonian activity with a potency superior to those of two further, preferential D, receptor agonists, pramipexole and ropinirole. However, potential neuroprotective properties of S32054 have not, to date, been evaluated. Herein, employing several measures of cellular integrity, we demonstrate that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SYSY cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro. Further, S32504 was substantially more potent than pramipexole and ropinirole, the latter of which was neurotoxic at high concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5 mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the substantia nigra pars compacta and ventral tegmental area. A high dose of ropinirole (2.5 mg/kg) provided some protection but statistical significance was not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded protection against the MPTP-induced loss of DA fibers in the striatum, as measured by TH-IR and dopamine transporter immunoreactive fiber counts. In conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly protects dopaminergic neurones against the neurotoxic effects of MPP⁺ and MPTP in in vitro and in vivo models, respectively. The underlying mechanisms and therapeutic pertinence of these actions will be of interest to further evaluate in view of its potent actions in behavioral models of antiparkinson activity.

A01	`01`	`1`		`@0 0014-4886`
A02	`01`			`@0 EXNEAC`
A03		`1`		`@0 Exp. neurol. : (Print)`
A05				`@2 184`
A06				`@2 1`
A08	`01`	`1`	`ENG`	`@1 Neuroprotective effects of the novel D₃/D₂ receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole`
A11	`01`	`1`		`@1 JOYCE (Jeffrey N.)`
A11	`02`	`1`		`@1 PRESGRAVES (Steve)`
A11	`03`	`1`		`@1 RENISH (Lynn)`
A11	`04`	`1`		`@1 BORWEGE (Sabinne)`
A11	`05`	`1`		`@1 OSREDKAR (Tracy)`
A11	`06`	`1`		`@1 HAGNER (Diane)`
A11	`07`	`1`		`@1 REPLOGLE (Maria)`
A11	`08`	`1`		`@1 PAZSOLDAN (Mateo)`
A11	`09`	`1`		`@1 MILLAN (Mark J.)`
A14	`01`			`@1 Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute @2 Sun City, AZ 852622 @3 USA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 5 aut. @Z 6 aut. @Z 7 aut. @Z 8 aut.`
A14	`02`			`@1 Department of Psychopharmacology, Institut de recherches de Servier, 125 chemin de ronde @2 78290 Croissy-sur-Seine (Paris) @3 FRA @Z 9 aut.`
A20				`@1 393-407`
A21				`@1 2003`
A23	`01`			`@0 ENG`
A43	`01`			`@1 INIST @2 9181 @5 354000118845000410`
A44				`@0 0000 @1 © 2004 INIST-CNRS. All rights reserved.`
A45				`@0 2 p.1/4`
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A60				`@1 P`
A61				`@0 A`
A64	`01`	`1`		`@0 Experimental neurology : (Print)`
A66	`01`			`@0 USA`
C01	`01`		`ENG`	@0 The novel naphtoxazine derivative and preferential D, vs D₂ receptor agonist, S32504, restores perturbed motor function in rodent and primate models of antiparkinsonian activity with a potency superior to those of two further, preferential D, receptor agonists, pramipexole and ropinirole. However, potential neuroprotective properties of S32054 have not, to date, been evaluated. Herein, employing several measures of cellular integrity, we demonstrate that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SYSY cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro. Further, S32504 was substantially more potent than pramipexole and ropinirole, the latter of which was neurotoxic at high concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5 mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the substantia nigra pars compacta and ventral tegmental area. A high dose of ropinirole (2.5 mg/kg) provided some protection but statistical significance was not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded protection against the MPTP-induced loss of DA fibers in the striatum, as measured by TH-IR and dopamine transporter immunoreactive fiber counts. In conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly protects dopaminergic neurones against the neurotoxic effects of MPP⁺ and MPTP in in vitro and in vivo models, respectively. The underlying mechanisms and therapeutic pertinence of these actions will be of interest to further evaluate in view of its potent actions in behavioral models of antiparkinson activity.
C02	`01`	`X`		`@0 002B17`
C03	`01`	`X`	`FRE`	`@0 Parkinson maladie @5 01`
C03	`01`	`X`	`ENG`	`@0 Parkinson disease @5 01`
C03	`01`	`X`	`SPA`	`@0 Parkinson enfermedad @5 01`
C03	`02`	`X`	`FRE`	`@0 Récepteur dopaminergique D3 @5 02`
C03	`02`	`X`	`ENG`	`@0 D3 Dopamine receptor @5 02 @6 «D3» Dopamine receptor`
C03	`02`	`X`	`SPA`	`@0 Receptor dopaminérgico D3 @5 02`
C03	`03`	`X`	`FRE`	`@0 Récepteur dopaminergique D2 @5 03`
C03	`03`	`X`	`ENG`	`@0 D2 Dopamine receptor @5 03 @6 «D2» Dopamine receptor`
C03	`03`	`X`	`SPA`	`@0 Receptor dopaminérgico D2 @5 03`
C03	`04`	`X`	`FRE`	`@0 Système nerveux pathologie @5 04`
C03	`04`	`X`	`ENG`	`@0 Nervous system diseases @5 04`
C03	`04`	`X`	`SPA`	`@0 Sistema nervioso patología @5 04`
C03	`05`	`X`	`FRE`	`@0 Antiparkinsonien @5 05`
C03	`05`	`X`	`ENG`	`@0 Antiparkinson agent @5 05`
C03	`05`	`X`	`SPA`	`@0 Antiparkinsoniano @5 05`
C03	`06`	`X`	`FRE`	`@0 In vitro @5 06`
C03	`06`	`X`	`ENG`	`@0 In vitro @5 06`
C03	`06`	`X`	`SPA`	`@0 In vitro @5 06`
C03	`07`	`X`	`FRE`	`@0 Etude comparative @5 08`
C03	`07`	`X`	`ENG`	`@0 Comparative study @5 08`
C03	`07`	`X`	`SPA`	`@0 Estudio comparativo @5 08`
C03	`08`	`X`	`FRE`	`@0 Ropinirole @2 NK @2 FR @5 09`
C03	`08`	`X`	`ENG`	`@0 Ropinirole @2 NK @2 FR @5 09`
C03	`08`	`X`	`SPA`	`@0 Ropinirol @2 NK @2 FR @5 09`
C03	`09`	`X`	`FRE`	`@0 Dérivée @5 11`
C03	`09`	`X`	`ENG`	`@0 Derivative @5 11`
C03	`09`	`X`	`SPA`	`@0 Derivada @5 11`
C03	`10`	`X`	`FRE`	`@0 Animal @5 12`
C03	`10`	`X`	`ENG`	`@0 Animal @5 12`
C03	`10`	`X`	`SPA`	`@0 Animal @5 12`
C03	`11`	`X`	`FRE`	`@0 Primates @2 NS @5 14`
C03	`11`	`X`	`ENG`	`@0 Primates @2 NS @5 14`
C03	`11`	`X`	`SPA`	`@0 Primates @2 NS @5 14`
C03	`12`	`X`	`FRE`	`@0 Modèle @5 15`
C03	`12`	`X`	`ENG`	`@0 Models @5 15`
C03	`12`	`X`	`SPA`	`@0 Modelo @5 15`
C03	`13`	`X`	`FRE`	`@0 Pramipexole @2 NK @2 FR @5 17`
C03	`13`	`X`	`ENG`	`@0 Pramipexole @2 NK @2 FR @5 17`
C03	`13`	`X`	`SPA`	`@0 Pramipexol @2 NK @2 FR @5 17`
C03	`14`	`X`	`FRE`	`@0 Mort cellulaire @5 18`
C03	`14`	`X`	`ENG`	`@0 Cell death @5 18`
C03	`14`	`X`	`SPA`	`@0 Muerte celular @5 18`
C03	`15`	`X`	`FRE`	`@0 Subchronique @5 19`
C03	`15`	`X`	`ENG`	`@0 Subchronic @5 19`
C03	`15`	`X`	`SPA`	`@0 Subcrónico @5 19`
C03	`16`	`X`	`FRE`	`@0 Traitement @5 20`
C03	`16`	`X`	`ENG`	`@0 Treatment @5 20`
C03	`16`	`X`	`SPA`	`@0 Tratamiento @5 20`
C03	`17`	`X`	`FRE`	`@0 Souris @5 21`
C03	`17`	`X`	`ENG`	`@0 Mouse @5 21`
C03	`17`	`X`	`SPA`	`@0 Ratón @5 21`
C03	`18`	`X`	`FRE`	`@0 Tyrosine 3-monooxygenase @2 FE @5 22 @6 Tyrosine «3»-monooxygenase`
C03	`18`	`X`	`ENG`	`@0 Tyrosine 3-monooxygenase @2 FE @5 22 @6 Tyrosine «3»-monooxygenase`
C03	`18`	`X`	`SPA`	`@0 Tyrosine 3-monooxygenase @2 FE @5 22 @6 Tyrosine «3»-monooxygenase`
C03	`19`	`X`	`FRE`	`@0 Locus niger @5 23`
C03	`19`	`X`	`ENG`	`@0 Locus niger @5 23`
C03	`19`	`X`	`SPA`	`@0 Locus níger @5 23`
C03	`20`	`X`	`FRE`	`@0 Aire tegmentaire ventrale @5 24`
C03	`20`	`X`	`ENG`	`@0 Ventral tegmental area @5 24`
C03	`20`	`X`	`SPA`	`@0 Area tegmental ventral @5 24`
C03	`21`	`X`	`FRE`	`@0 Dose forte @5 35`
C03	`21`	`X`	`ENG`	`@0 High dose @5 35`
C03	`21`	`X`	`SPA`	`@0 Dosis fuerte @5 35`
C07	`01`	`X`	`FRE`	`@0 Mammalia @2 NS`
C07	`01`	`X`	`ENG`	`@0 Mammalia @2 NS`
C07	`01`	`X`	`SPA`	`@0 Mammalia @2 NS`
C07	`02`	`X`	`FRE`	`@0 Vertebrata @2 NS`
C07	`02`	`X`	`ENG`	`@0 Vertebrata @2 NS`
C07	`02`	`X`	`SPA`	`@0 Vertebrata @2 NS`
C07	`03`	`X`	`FRE`	`@0 Rodentia @2 NS`
C07	`03`	`X`	`ENG`	`@0 Rodentia @2 NS`
C07	`03`	`X`	`SPA`	`@0 Rodentia @2 NS`
C07	`04`	`X`	`FRE`	`@0 Oxidoreductases @2 FE`
C07	`04`	`X`	`ENG`	`@0 Oxidoreductases @2 FE`
C07	`04`	`X`	`SPA`	`@0 Oxidoreductases @2 FE`
C07	`05`	`X`	`FRE`	`@0 Enzyme @2 FE`
C07	`05`	`X`	`ENG`	`@0 Enzyme @2 FE`
C07	`05`	`X`	`SPA`	`@0 Enzima @2 FE`
C07	`06`	`X`	`FRE`	`@0 Encéphale pathologie @5 37`
C07	`06`	`X`	`ENG`	`@0 Cerebral disorder @5 37`
C07	`06`	`X`	`SPA`	`@0 Encéfalo patología @5 37`
C07	`07`	`X`	`FRE`	`@0 Système nerveux central @5 38`
C07	`07`	`X`	`ENG`	`@0 Central nervous system @5 38`
C07	`07`	`X`	`SPA`	`@0 Sistema nervioso central @5 38`
C07	`08`	`X`	`FRE`	`@0 Catécholamine @5 39`
C07	`08`	`X`	`ENG`	`@0 Catecholamine @5 39`
C07	`08`	`X`	`SPA`	`@0 Catecolamina @5 39`
C07	`09`	`X`	`FRE`	`@0 Neurotransmetteur @5 40`
C07	`09`	`X`	`ENG`	`@0 Neurotransmitter @5 40`
C07	`09`	`X`	`SPA`	`@0 Neurotransmisor @5 40`
C07	`10`	`X`	`FRE`	`@0 Extrapyramidal syndrome @5 41`
C07	`10`	`X`	`ENG`	`@0 Extrapyramidal syndrome @5 41`
C07	`10`	`X`	`SPA`	`@0 Extrapiramidal síndrome @5 41`
C07	`11`	`X`	`FRE`	`@0 Maladie dégénérative @5 42`
C07	`11`	`X`	`ENG`	`@0 Degenerative disease @5 42`
C07	`11`	`X`	`SPA`	`@0 Enfermedad degenerativa @5 42`
C07	`12`	`X`	`FRE`	`@0 Système nerveux central pathologie @5 43`
C07	`12`	`X`	`ENG`	`@0 Central nervous system disease @5 43`
C07	`12`	`X`	`SPA`	`@0 Sistema nervosio central patología @5 43`
N21				`@1 173`
N44	`01`			`@1 OTO`
N82				`@1 OTO`

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<author><name sortKey="Replogle, Maria" sort="Replogle, Maria" uniqKey="Replogle M" first="Maria" last="Replogle">Maria Replogle</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Neuroprotective effects of the novel D<sub>3</sub>
/D<sub>2</sub>
 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole</title>
<author><name sortKey="Joyce, Jeffrey N" sort="Joyce, Jeffrey N" uniqKey="Joyce J" first="Jeffrey N." last="Joyce">Jeffrey N. Joyce</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
<s2>Sun City, AZ 852622</s2>
<s3>USA</s3>
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<author><name sortKey="Presgraves, Steve" sort="Presgraves, Steve" uniqKey="Presgraves S" first="Steve" last="Presgraves">Steve Presgraves</name>
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<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
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<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
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<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
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<author><name sortKey="Replogle, Maria" sort="Replogle, Maria" uniqKey="Replogle M" first="Maria" last="Replogle">Maria Replogle</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
<s2>Sun City, AZ 852622</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<author><name sortKey="Pazsoldan, Mateo" sort="Pazsoldan, Mateo" uniqKey="Pazsoldan M" first="Mateo" last="Pazsoldan">Mateo Pazsoldan</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
<s2>Sun City, AZ 852622</s2>
<s3>USA</s3>
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<author><name sortKey="Millan, Mark J" sort="Millan, Mark J" uniqKey="Millan M" first="Mark J." last="Millan">Mark J. Millan</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Psychopharmacology, Institut de recherches de Servier, 125 chemin de ronde</s1>
<s2>78290 Croissy-sur-Seine (Paris)</s2>
<s3>FRA</s3>
<sZ>9 aut.</sZ>
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<country>France</country>
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<series><title level="j" type="main">Experimental neurology : (Print)</title>
<title level="j" type="abbreviated">Exp. neurol. : (Print)</title>
<idno type="ISSN">0014-4886</idno>
<imprint><date when="2003">2003</date>
</imprint>
</series>
</biblStruct>
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<seriesStmt><title level="j" type="main">Experimental neurology : (Print)</title>
<title level="j" type="abbreviated">Exp. neurol. : (Print)</title>
<idno type="ISSN">0014-4886</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term>
<term>Antiparkinson agent</term>
<term>Cell death</term>
<term>Comparative study</term>
<term>D2 Dopamine receptor</term>
<term>D3 Dopamine receptor</term>
<term>Derivative</term>
<term>High dose</term>
<term>In vitro</term>
<term>Locus niger</term>
<term>Models</term>
<term>Mouse</term>
<term>Nervous system diseases</term>
<term>Parkinson disease</term>
<term>Pramipexole</term>
<term>Primates</term>
<term>Ropinirole</term>
<term>Subchronic</term>
<term>Treatment</term>
<term>Tyrosine 3-monooxygenase</term>
<term>Ventral tegmental area</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Parkinson maladie</term>
<term>Récepteur dopaminergique D3</term>
<term>Récepteur dopaminergique D2</term>
<term>Système nerveux pathologie</term>
<term>Antiparkinsonien</term>
<term>In vitro</term>
<term>Etude comparative</term>
<term>Ropinirole</term>
<term>Dérivée</term>
<term>Animal</term>
<term>Primates</term>
<term>Modèle</term>
<term>Pramipexole</term>
<term>Mort cellulaire</term>
<term>Subchronique</term>
<term>Traitement</term>
<term>Souris</term>
<term>Tyrosine 3-monooxygenase</term>
<term>Locus niger</term>
<term>Aire tegmentaire ventrale</term>
<term>Dose forte</term>
</keywords>
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<front><div type="abstract" xml:lang="en">The novel naphtoxazine derivative and preferential D, vs D<sub>2</sub>
 receptor agonist, S32504, restores perturbed motor function in rodent and primate models of antiparkinsonian activity with a potency superior to those of two further, preferential D, receptor agonists, pramipexole and ropinirole. However, potential neuroprotective properties of S32054 have not, to date, been evaluated. Herein, employing several measures of cellular integrity, we demonstrate that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SYSY cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro. Further, S32504 was substantially more potent than pramipexole and ropinirole, the latter of which was neurotoxic at high concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5 mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the substantia nigra pars compacta and ventral tegmental area. A high dose of ropinirole (2.5 mg/kg) provided some protection but statistical significance was not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded protection against the MPTP-induced loss of DA fibers in the striatum, as measured by TH-IR and dopamine transporter immunoreactive fiber counts. In conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly protects dopaminergic neurones against the neurotoxic effects of MPP<sup>+</sup>
 and MPTP in in vitro and in vivo models, respectively. The underlying mechanisms and therapeutic pertinence of these actions will be of interest to further evaluate in view of its potent actions in behavioral models of antiparkinson activity.</div>
</front>
</TEI>
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<fA08 i1="01" i2="1" l="ENG"><s1>Neuroprotective effects of the novel D<sub>3</sub>
/D<sub>2</sub>
 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>JOYCE (Jeffrey N.)</s1>
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<fA11 i1="02" i2="1"><s1>PRESGRAVES (Steve)</s1>
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<fA11 i1="03" i2="1"><s1>RENISH (Lynn)</s1>
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<fA11 i1="04" i2="1"><s1>BORWEGE (Sabinne)</s1>
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<fA11 i1="05" i2="1"><s1>OSREDKAR (Tracy)</s1>
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<fA11 i1="06" i2="1"><s1>HAGNER (Diane)</s1>
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<fA11 i1="07" i2="1"><s1>REPLOGLE (Maria)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>PAZSOLDAN (Mateo)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>MILLAN (Mark J.)</s1>
</fA11>
<fA14 i1="01"><s1>Thomas H. Christopher Center for Parkinson's Diseuse Research, Sun Health Research Institute</s1>
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<s3>USA</s3>
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<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Department of Psychopharmacology, Institut de recherches de Servier, 125 chemin de ronde</s1>
<s2>78290 Croissy-sur-Seine (Paris)</s2>
<s3>FRA</s3>
<sZ>9 aut.</sZ>
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<fC01 i1="01" l="ENG"><s0>The novel naphtoxazine derivative and preferential D, vs D<sub>2</sub>
 receptor agonist, S32504, restores perturbed motor function in rodent and primate models of antiparkinsonian activity with a potency superior to those of two further, preferential D, receptor agonists, pramipexole and ropinirole. However, potential neuroprotective properties of S32054 have not, to date, been evaluated. Herein, employing several measures of cellular integrity, we demonstrate that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SYSY cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro. Further, S32504 was substantially more potent than pramipexole and ropinirole, the latter of which was neurotoxic at high concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5 mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the substantia nigra pars compacta and ventral tegmental area. A high dose of ropinirole (2.5 mg/kg) provided some protection but statistical significance was not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded protection against the MPTP-induced loss of DA fibers in the striatum, as measured by TH-IR and dopamine transporter immunoreactive fiber counts. In conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly protects dopaminergic neurones against the neurotoxic effects of MPP<sup>+</sup>
 and MPTP in in vitro and in vivo models, respectively. The underlying mechanisms and therapeutic pertinence of these actions will be of interest to further evaluate in view of its potent actions in behavioral models of antiparkinson activity.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B17</s0>
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<s5>01</s5>
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<s5>02</s5>
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<fC03 i1="02" i2="X" l="ENG"><s0>D3 Dopamine receptor</s0>
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<s6>«D3» Dopamine receptor</s6>
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<fC03 i1="02" i2="X" l="SPA"><s0>Receptor dopaminérgico D3</s0>
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<s5>03</s5>
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<fC03 i1="03" i2="X" l="ENG"><s0>D2 Dopamine receptor</s0>
<s5>03</s5>
<s6>«D2» Dopamine receptor</s6>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Receptor dopaminérgico D2</s0>
<s5>03</s5>
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<s5>06</s5>
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<s5>08</s5>
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<s2>FR</s2>
<s5>09</s5>
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<s2>NK</s2>
<s2>FR</s2>
<s5>09</s5>
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<fC03 i1="10" i2="X" l="FRE"><s0>Animal</s0>
<s5>12</s5>
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<s5>12</s5>
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<fC03 i1="10" i2="X" l="SPA"><s0>Animal</s0>
<s5>12</s5>
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<s2>NS</s2>
<s5>14</s5>
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<s5>14</s5>
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<s5>20</s5>
</fC03>
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<s5>21</s5>
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<s5>22</s5>
<s6>Tyrosine «3»-monooxygenase</s6>
</fC03>
<fC03 i1="18" i2="X" l="ENG"><s0>Tyrosine 3-monooxygenase</s0>
<s2>FE</s2>
<s5>22</s5>
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<fC03 i1="18" i2="X" l="SPA"><s0>Tyrosine 3-monooxygenase</s0>
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<s5>22</s5>
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<s5>23</s5>
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<s5>23</s5>
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<fC03 i1="19" i2="X" l="SPA"><s0>Locus níger</s0>
<s5>23</s5>
</fC03>
<fC03 i1="20" i2="X" l="FRE"><s0>Aire tegmentaire ventrale</s0>
<s5>24</s5>
</fC03>
<fC03 i1="20" i2="X" l="ENG"><s0>Ventral tegmental area</s0>
<s5>24</s5>
</fC03>
<fC03 i1="20" i2="X" l="SPA"><s0>Area tegmental ventral</s0>
<s5>24</s5>
</fC03>
<fC03 i1="21" i2="X" l="FRE"><s0>Dose forte</s0>
<s5>35</s5>
</fC03>
<fC03 i1="21" i2="X" l="ENG"><s0>High dose</s0>
<s5>35</s5>
</fC03>
<fC03 i1="21" i2="X" l="SPA"><s0>Dosis fuerte</s0>
<s5>35</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Encéphale pathologie</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Cerebral disorder</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Encéfalo patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Système nerveux central</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Central nervous system</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Sistema nervioso central</s0>
<s5>38</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Catécholamine</s0>
<s5>39</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Catecholamine</s0>
<s5>39</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Catecolamina</s0>
<s5>39</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Neurotransmetteur</s0>
<s5>40</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Neurotransmitter</s0>
<s5>40</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Neurotransmisor</s0>
<s5>40</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0>
<s5>41</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0>
<s5>41</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0>
<s5>41</s5>
</fC07>
<fC07 i1="11" i2="X" l="FRE"><s0>Maladie dégénérative</s0>
<s5>42</s5>
</fC07>
<fC07 i1="11" i2="X" l="ENG"><s0>Degenerative disease</s0>
<s5>42</s5>
</fC07>
<fC07 i1="11" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0>
<s5>42</s5>
</fC07>
<fC07 i1="12" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0>
<s5>43</s5>
</fC07>
<fC07 i1="12" i2="X" l="ENG"><s0>Central nervous system disease</s0>
<s5>43</s5>
</fC07>
<fC07 i1="12" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0>
<s5>43</s5>
</fC07>
<fN21><s1>173</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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	La maladie de Parkinson en France (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 en France (serveur d'exploration)

Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole

Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole

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