Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function.
Identifieur interne : 000330 ( Ncbi/Merge ); précédent : 000329; suivant : 000331Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function.
Auteurs : Erwan Bézard [France] ; Sandrine Ferry ; Ulrich Mach ; Holger Stark ; Ludovic Leriche ; Thomas Boraud ; Christian Gross ; Pierre SokoloffSource :
- Nature medicine [ 1078-8956 ] ; 2003.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (metabolism), Acrylamides (pharmacology), Animals, Antiparkinson Agents (therapeutic use), Antiparkinson Agents (toxicity), Dopamine Agents (metabolism), Dopamine Agents (toxicity), Dopamine Antagonists (pharmacology), Dyskinesia, Drug-Induced, Female, Haplorhini, Humans, Isoquinolines (pharmacology), Levodopa (therapeutic use), Levodopa (toxicity), MPTP Poisoning (drug therapy), MPTP Poisoning (metabolism), Molecular Structure, Motor Activity (drug effects), Naphthalenes (pharmacology), Neostriatum (cytology), Neostriatum (drug effects), Neostriatum (metabolism), Piperazines (pharmacology), Pyrrolidines (pharmacology), Rats, Receptors, Dopamine D2 (agonists), Receptors, Dopamine D2 (metabolism), Receptors, Dopamine D3.
- MESH :
- chemical , agonists : Receptors, Dopamine D2.
- chemical , metabolism : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dopamine Agents, Receptors, Dopamine D2.
- chemical , pharmacology : Acrylamides, Dopamine Antagonists, Isoquinolines, Naphthalenes, Piperazines, Pyrrolidines.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- chemical , toxicity : Antiparkinson Agents, Dopamine Agents, Levodopa.
- cytology : Neostriatum.
- drug effects : Motor Activity, Neostriatum.
- drug therapy : MPTP Poisoning.
- metabolism : MPTP Poisoning, Neostriatum.
- Animals, Dyskinesia, Drug-Induced, Female, Haplorhini, Humans, Molecular Structure, Rats, Receptors, Dopamine D3.
Abstract
In monkeys rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), expression of the dopamine D3 receptor was decreased. However, levodopa-induced dyskinesia (LID), similar to the debilitating and pharmacoresistant involuntary movements elicited after long-term treatment with levodopa in patients with Parkinson disease (PD), was associated with overexpression of this receptor. Administration of a D3 receptor-selective partial agonist strongly attenuated levodopa-induced dyskinesia, but left unaffected the therapeutic effect of levodopa. In contrast, attenuation of dyskinesia by D3 receptor antagonists was accompanied by the reappearance of PD-like symptoms. These results indicated that the D3 receptor participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D3 receptor function and correct side effects of levodopa therapy in patients with PD.
DOI: 10.1038/nm875
PubMed: 12740572
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However, levodopa-induced dyskinesia (LID), similar to the debilitating and pharmacoresistant involuntary movements elicited after long-term treatment with levodopa in patients with Parkinson disease (PD), was associated with overexpression of this receptor. Administration of a D3 receptor-selective partial agonist strongly attenuated levodopa-induced dyskinesia, but left unaffected the therapeutic effect of levodopa. In contrast, attenuation of dyskinesia by D3 receptor antagonists was accompanied by the reappearance of PD-like symptoms. These results indicated that the D3 receptor participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D3 receptor function and correct side effects of levodopa therapy in patients with PD.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12740572</PMID><DateCreated><Year>2003</Year><Month>06</Month><Day>02</Day></DateCreated><DateCompleted><Year>2003</Year><Month>08</Month><Day>14</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">1078-8956</ISSN><JournalIssue CitedMedium="Print"><Volume>9</Volume><Issue>6</Issue><PubDate><Year>2003</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Nature medicine</Title><ISOAbbreviation>Nat. 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These results indicated that the D3 receptor participated in both dyskinesia and the therapeutic action of levodopa, and that partial agonists may normalize D3 receptor function and correct side effects of levodopa therapy in patients with PD.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bézard</LastName><ForeName>Erwan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Segalen, 33076 Bordeaux, France. erwan.bezard@umr5543.u-bordeaux2.fr</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferry</LastName><ForeName>Sandrine</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Mach</LastName><ForeName>Ulrich</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Stark</LastName><ForeName>Holger</ForeName><Initials>H</Initials></Author><Author 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IdType="pii">nm875</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Aquitaine</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Bordeaux</li></settlement></list><tree><noCountry><name sortKey="Boraud, Thomas" sort="Boraud, Thomas" uniqKey="Boraud T" first="Thomas" last="Boraud">Thomas Boraud</name><name sortKey="Ferry, Sandrine" sort="Ferry, Sandrine" uniqKey="Ferry S" first="Sandrine" last="Ferry">Sandrine Ferry</name><name sortKey="Gross, Christian" sort="Gross, Christian" uniqKey="Gross C" first="Christian" last="Gross">Christian Gross</name><name sortKey="Leriche, Ludovic" sort="Leriche, Ludovic" uniqKey="Leriche L" first="Ludovic" last="Leriche">Ludovic Leriche</name><name sortKey="Mach, Ulrich" sort="Mach, Ulrich" uniqKey="Mach U" first="Ulrich" last="Mach">Ulrich Mach</name><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name><name sortKey="Stark, Holger" sort="Stark, Holger" uniqKey="Stark H" first="Holger" last="Stark">Holger Stark</name></noCountry><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bézard">Erwan Bézard</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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