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

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Selective blockade of D3 dopamine receptors enhances the anti-parkinsonian properties of ropinirole and levodopa in the MPTP-lesioned primate

Identifieur interne : 000847 ( PascalFrancis/Checkpoint ); précédent : 000846; suivant : 000848

Selective blockade of D3 dopamine receptors enhances the anti-parkinsonian properties of ropinirole and levodopa in the MPTP-lesioned primate

Auteurs : M. A. Silverdale [Royaume-Uni] ; S. L. Nicholson [Royaume-Uni] ; P. Ravenscroft [Royaume-Uni] ; A. R. Crossman [Royaume-Uni] ; M. J. Millan [France] ; J. M. Brotchie [Canada]

Source :

RBID : Pascal:05-0003811

Descripteurs français

English descriptors

Abstract

To date, the lack of highly selective antagonists at the dopamine D3receptor has hampered clarification of their involvement in the actions of currently used therapies in Parkinson's disease. However, the novel benzopyranopyrrole, S33084, displays greater than 100-fold selectivity as an antagonist for D3 versus D2 receptors and all other sites tested. S33084 was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets previously primed with levodopa to elicit dyskinesia. Administered alone, S33084 exerted a modest, but significant, anti-parkinsonian effect without provoking dyskinesia. At low D3-selective doses (0.16 and 0.64 mg/kg), S33084 potentiated, though to different extents and in qualitatively different ways, the anti-parkinsonian actions of both ropinirole and levodopa. At these doses. S33084 did not significantly modify levodopa-induced or ropinirole-induced dyskinesia. These data suggest that ropinirole and levodopa do not exert their anti-parkinsonian or pro-dyskinetic actions via D3 receptor stimulation. Indeed, stimulation of D3 receptors may be detrimental to the anti-parkinsonian properties of D2/D3 agonists. Selectivity for stimulation of D2, over D3, receptors may therefore be a beneficial property of dopamine receptor agonists in management of motor symptoms of Parkinson's disease patients with established dyskinesia.


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Pascal:05-0003811

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<div type="abstract" xml:lang="en">To date, the lack of highly selective antagonists at the dopamine D
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<sub>3</sub>
versus D
<sub>2</sub>
receptors and all other sites tested. S33084 was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets previously primed with levodopa to elicit dyskinesia. Administered alone, S33084 exerted a modest, but significant, anti-parkinsonian effect without provoking dyskinesia. At low D
<sub>3</sub>
-selective doses (0.16 and 0.64 mg/kg), S33084 potentiated, though to different extents and in qualitatively different ways, the anti-parkinsonian actions of both ropinirole and levodopa. At these doses. S33084 did not significantly modify levodopa-induced or ropinirole-induced dyskinesia. These data suggest that ropinirole and levodopa do not exert their anti-parkinsonian or pro-dyskinetic actions via D
<sub>3</sub>
receptor stimulation. Indeed, stimulation of D
<sub>3</sub>
receptors may be detrimental to the anti-parkinsonian properties of D
<sub>2</sub>
/D
<sub>3</sub>
agonists. Selectivity for stimulation of D
<sub>2</sub>
, over D
<sub>3</sub>
, receptors may therefore be a beneficial property of dopamine receptor agonists in management of motor symptoms of Parkinson's disease patients with established dyskinesia.</div>
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versus D
<sub>2</sub>
receptors and all other sites tested. S33084 was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets previously primed with levodopa to elicit dyskinesia. Administered alone, S33084 exerted a modest, but significant, anti-parkinsonian effect without provoking dyskinesia. At low D
<sub>3</sub>
-selective doses (0.16 and 0.64 mg/kg), S33084 potentiated, though to different extents and in qualitatively different ways, the anti-parkinsonian actions of both ropinirole and levodopa. At these doses. S33084 did not significantly modify levodopa-induced or ropinirole-induced dyskinesia. These data suggest that ropinirole and levodopa do not exert their anti-parkinsonian or pro-dyskinetic actions via D
<sub>3</sub>
receptor stimulation. Indeed, stimulation of D
<sub>3</sub>
receptors may be detrimental to the anti-parkinsonian properties of D
<sub>2</sub>
/D
<sub>3</sub>
agonists. Selectivity for stimulation of D
<sub>2</sub>
, over D
<sub>3</sub>
, receptors may therefore be a beneficial property of dopamine receptor agonists in management of motor symptoms of Parkinson's disease patients with established dyskinesia.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002B02U01</s0>
</fC02>
<fC02 i1="02" i2="X">
<s0>002B02B06</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Parkinson maladie</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Parkinson disease</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Parkinson enfermedad</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Récepteur dopaminergique D3</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>D3 Dopamine receptor</s0>
<s5>02</s5>
<s6>«D3» Dopamine receptor</s6>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Receptor dopaminérgico D3</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Ropinirole</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Ropinirole</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Ropinirol</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>Lévodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Primates</s0>
<s2>NS</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Primates</s0>
<s2>NS</s2>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Primates</s0>
<s2>NS</s2>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Antagoniste dopamine</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Dopamine antagonist</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Antagonista dopamina</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Traitement</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>Treatment</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Tratamiento</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE">
<s0>Sélectivité</s0>
<s5>11</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG">
<s0>Selectivity</s0>
<s5>11</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA">
<s0>Selectividad</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE">
<s0>Etude comparative</s0>
<s5>12</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG">
<s0>Comparative study</s0>
<s5>12</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA">
<s0>Estudio comparativo</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE">
<s0>Récepteur dopaminergique D2</s0>
<s5>14</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG">
<s0>D2 Dopamine receptor</s0>
<s5>14</s5>
<s6>«D2» Dopamine receptor</s6>
</fC03>
<fC03 i1="11" i2="X" l="SPA">
<s0>Receptor dopaminérgico D2</s0>
<s5>14</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE">
<s0>Dose faible</s0>
<s5>15</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG">
<s0>Low dose</s0>
<s5>15</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA">
<s0>Dosis débil</s0>
<s5>15</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE">
<s0>Récepteur dopaminergique</s0>
<s5>17</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG">
<s0>Dopamine receptor</s0>
<s5>17</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA">
<s0>Receptor dopaminérgico</s0>
<s5>17</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE">
<s0>Stimulant dopaminergique</s0>
<s5>18</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG">
<s0>Dopamine agonist</s0>
<s5>18</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA">
<s0>Estimulante dopaminérgico</s0>
<s5>18</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE">
<s0>Conduite à tenir</s0>
<s5>19</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG">
<s0>Clinical management</s0>
<s5>19</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA">
<s0>Actitud médica</s0>
<s5>19</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE">
<s0>Homme</s0>
<s5>20</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG">
<s0>Human</s0>
<s5>20</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA">
<s0>Hombre</s0>
<s5>20</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE">
<s0>Dopamine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>21</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG">
<s0>Dopamine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>21</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA">
<s0>Dopamina</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>21</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE">
<s0>Noyau gris central</s0>
<s5>22</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG">
<s0>Basal ganglion</s0>
<s5>22</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA">
<s0>Núcleo basal</s0>
<s5>22</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE">
<s0>Contrôle moteur</s0>
<s5>25</s5>
</fC03>
<fC03 i1="19" i2="X" l="ENG">
<s0>Motor control</s0>
<s5>25</s5>
</fC03>
<fC03 i1="19" i2="X" l="SPA">
<s0>Control motor</s0>
<s5>25</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>Encéphale pathologie</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Cerebral disorder</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Encéfalo patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Extrapyramidal syndrome</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Extrapyramidal syndrome</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Extrapiramidal síndrome</s0>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Maladie dégénérative</s0>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Degenerative disease</s0>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Enfermedad degenerativa</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Système nerveux central pathologie</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Central nervous system disease</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Sistema nervosio central patología</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Système nerveux pathologie</s0>
<s5>41</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Nervous system diseases</s0>
<s5>41</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Sistema nervioso patología</s0>
<s5>41</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE">
<s0>Antiparkinsonien</s0>
<s5>42</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG">
<s0>Antiparkinson agent</s0>
<s5>42</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA">
<s0>Antiparkinsoniano</s0>
<s5>42</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE">
<s0>Mouvement involontaire</s0>
<s5>43</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG">
<s0>Involuntary movement</s0>
<s5>43</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA">
<s0>Movimiento involuntario</s0>
<s5>43</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE">
<s0>Trouble neurologique</s0>
<s5>45</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG">
<s0>Neurological disorder</s0>
<s5>45</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA">
<s0>Trastorno neurológico</s0>
<s5>45</s5>
</fC07>
<fC07 i1="11" i2="X" l="FRE">
<s0>Catécholamine</s0>
<s5>46</s5>
</fC07>
<fC07 i1="11" i2="X" l="ENG">
<s0>Catecholamine</s0>
<s5>46</s5>
</fC07>
<fC07 i1="11" i2="X" l="SPA">
<s0>Catecolamina</s0>
<s5>46</s5>
</fC07>
<fC07 i1="12" i2="X" l="FRE">
<s0>Neurotransmetteur</s0>
<s5>47</s5>
</fC07>
<fC07 i1="12" i2="X" l="ENG">
<s0>Neurotransmitter</s0>
<s5>47</s5>
</fC07>
<fC07 i1="12" i2="X" l="SPA">
<s0>Neurotransmisor</s0>
<s5>47</s5>
</fC07>
<fC07 i1="13" i2="X" l="FRE">
<s0>Système nerveux central</s0>
<s5>48</s5>
</fC07>
<fC07 i1="13" i2="X" l="ENG">
<s0>Central nervous system</s0>
<s5>48</s5>
</fC07>
<fC07 i1="13" i2="X" l="SPA">
<s0>Sistema nervioso central</s0>
<s5>48</s5>
</fC07>
<fN21>
<s1>004</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations>
<list>
<country>
<li>Canada</li>
<li>France</li>
<li>Royaume-Uni</li>
</country>
<region>
<li>Angleterre</li>
<li>Grand Manchester</li>
</region>
<settlement>
<li>Manchester</li>
</settlement>
<orgName>
<li>Université de Manchester</li>
</orgName>
</list>
<tree>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Silverdale, M A" sort="Silverdale, M A" uniqKey="Silverdale M" first="M. A." last="Silverdale">M. A. Silverdale</name>
</region>
<name sortKey="Crossman, A R" sort="Crossman, A R" uniqKey="Crossman A" first="A. R." last="Crossman">A. R. Crossman</name>
<name sortKey="Crossman, A R" sort="Crossman, A R" uniqKey="Crossman A" first="A. R." last="Crossman">A. R. Crossman</name>
<name sortKey="Nicholson, S L" sort="Nicholson, S L" uniqKey="Nicholson S" first="S. L." last="Nicholson">S. L. Nicholson</name>
<name sortKey="Ravenscroft, P" sort="Ravenscroft, P" uniqKey="Ravenscroft P" first="P." last="Ravenscroft">P. Ravenscroft</name>
<name sortKey="Ravenscroft, P" sort="Ravenscroft, P" uniqKey="Ravenscroft P" first="P." last="Ravenscroft">P. Ravenscroft</name>
<name sortKey="Silverdale, M A" sort="Silverdale, M A" uniqKey="Silverdale M" first="M. A." last="Silverdale">M. A. Silverdale</name>
</country>
<country name="France">
<noRegion>
<name sortKey="Millan, M J" sort="Millan, M J" uniqKey="Millan M" first="M. J." last="Millan">M. J. Millan</name>
</noRegion>
</country>
<country name="Canada">
<noRegion>
<name sortKey="Brotchie, J M" sort="Brotchie, J M" uniqKey="Brotchie J" first="J. M." last="Brotchie">J. M. Brotchie</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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   |wiki=    Wicri/Canada
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   |texte=   Selective blockade of D3 dopamine receptors enhances the anti-parkinsonian properties of ropinirole and levodopa in the MPTP-lesioned primate
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