Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys.
Identifieur interne : 000020 ( Ncbi/Merge ); précédent : 000019; suivant : 000021Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys.
Auteurs : R. Grondin [Canada] ; P J Bédard ; A. Hadj Tahar ; L. Grégoire ; A. Mori ; H. KaseSource :
- Neurology [ 0028-3878 ] ; 1999.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (adverse effects), Animals, Brain (drug effects), Female, Levodopa (pharmacology), Levodopa (therapeutic use), Locomotion (drug effects), Macaca fascicularis, Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (drug therapy), Purinergic P1 Receptor Antagonists, Purines (pharmacology), Purines (therapeutic use), Receptor, Adenosine A2A.
- MESH :
- chemical , adverse effects : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Brain, Locomotion.
- drug therapy : Parkinson Disease, Secondary.
- chemical , pharmacology : Levodopa, Purines.
- chemical , therapeutic use : Levodopa, Purines.
- Animals, Female, Macaca fascicularis, Purinergic P1 Receptor Antagonists, Receptor, Adenosine A2A.
Abstract
Chronic treatment with L-3,4-dihydroxyphenylalanine (L-dopa) is often associated with motor side effects in PD patients. The search for new therapeutic approaches has led to study the role of other neuromodulators including adenosine. Among the four adenosine receptors characterized so far, the A2A subtype is distinctively present on striatopallidal output neurons containing enkephalin and mainly bearing dopamine (DA) D2 receptors (indirect pathway). Studies in DA-denervated rats suggest that blockade of adenosine A2A receptors might be used in PD.
PubMed: 10331698
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys.</title><author><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R" last="Grondin">R. Grondin</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience Research Unit, Laval University Research Center, Quebec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Neuroscience Research Unit, Laval University Research Center, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P J" last="Bédard">P J Bédard</name></author><author><name sortKey="Hadj Tahar, A" sort="Hadj Tahar, A" uniqKey="Hadj Tahar A" first="A" last="Hadj Tahar">A. Hadj Tahar</name></author><author><name sortKey="Gregoire, L" sort="Gregoire, L" uniqKey="Gregoire L" first="L" last="Grégoire">L. Grégoire</name></author><author><name sortKey="Mori, A" sort="Mori, A" uniqKey="Mori A" first="A" last="Mori">A. Mori</name></author><author><name sortKey="Kase, H" sort="Kase, H" uniqKey="Kase H" first="H" last="Kase">H. Kase</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1999">1999</date><idno type="RBID">pubmed:10331698</idno><idno type="pmid">10331698</idno><idno type="wicri:Area/PubMed/Corpus">001712</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001712</idno><idno type="wicri:Area/PubMed/Curation">001712</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001712</idno><idno type="wicri:Area/PubMed/Checkpoint">001712</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001712</idno><idno type="wicri:Area/Ncbi/Merge">000020</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys.</title><author><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R" last="Grondin">R. Grondin</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience Research Unit, Laval University Research Center, Quebec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Neuroscience Research Unit, Laval University Research Center, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P J" last="Bédard">P J Bédard</name></author><author><name sortKey="Hadj Tahar, A" sort="Hadj Tahar, A" uniqKey="Hadj Tahar A" first="A" last="Hadj Tahar">A. Hadj Tahar</name></author><author><name sortKey="Gregoire, L" sort="Gregoire, L" uniqKey="Gregoire L" first="L" last="Grégoire">L. Grégoire</name></author><author><name sortKey="Mori, A" sort="Mori, A" uniqKey="Mori A" first="A" last="Mori">A. Mori</name></author><author><name sortKey="Kase, H" sort="Kase, H" uniqKey="Kase H" first="H" last="Kase">H. Kase</name></author></analytic><series><title level="j">Neurology</title><idno type="ISSN">0028-3878</idno><imprint><date when="1999" type="published">1999</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (adverse effects)</term><term>Animals</term><term>Brain (drug effects)</term><term>Female</term><term>Levodopa (pharmacology)</term><term>Levodopa (therapeutic use)</term><term>Locomotion (drug effects)</term><term>Macaca fascicularis</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (drug therapy)</term><term>Purinergic P1 Receptor Antagonists</term><term>Purines (pharmacology)</term><term>Purines (therapeutic use)</term><term>Receptor, Adenosine A2A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term><term>Locomotion</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Levodopa</term><term>Purines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Levodopa</term><term>Purines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Macaca fascicularis</term><term>Purinergic P1 Receptor Antagonists</term><term>Receptor, Adenosine A2A</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Chronic treatment with L-3,4-dihydroxyphenylalanine (L-dopa) is often associated with motor side effects in PD patients. The search for new therapeutic approaches has led to study the role of other neuromodulators including adenosine. Among the four adenosine receptors characterized so far, the A2A subtype is distinctively present on striatopallidal output neurons containing enkephalin and mainly bearing dopamine (DA) D2 receptors (indirect pathway). Studies in DA-denervated rats suggest that blockade of adenosine A2A receptors might be used in PD.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10331698</PMID><DateCreated><Year>1999</Year><Month>05</Month><Day>27</Day></DateCreated><DateCompleted><Year>1999</Year><Month>05</Month><Day>27</Day></DateCompleted><DateRevised><Year>2014</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0028-3878</ISSN><JournalIssue CitedMedium="Print"><Volume>52</Volume><Issue>8</Issue><PubDate><Year>1999</Year><Month>May</Month><Day>12</Day></PubDate></JournalIssue><Title>Neurology</Title><ISOAbbreviation>Neurology</ISOAbbreviation></Journal><ArticleTitle>Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys.</ArticleTitle><Pagination><MedlinePgn>1673-7</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Chronic treatment with L-3,4-dihydroxyphenylalanine (L-dopa) is often associated with motor side effects in PD patients. The search for new therapeutic approaches has led to study the role of other neuromodulators including adenosine. Among the four adenosine receptors characterized so far, the A2A subtype is distinctively present on striatopallidal output neurons containing enkephalin and mainly bearing dopamine (DA) D2 receptors (indirect pathway). Studies in DA-denervated rats suggest that blockade of adenosine A2A receptors might be used in PD.</AbstractText><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To evaluate the antiparkinsonian effect of a new selective adenosine A2A receptor antagonist, KW-6002, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">In the present study, we used six MPTP-exposed cynomolgus monkeys already primed and exhibiting L-dopa-induced dyskinesias to evaluate both the antiparkinsonian and dyskinetic effect upon challenge with two oral doses (60 and 90 mg/kg) of KW-6002 administered alone or in combination with L-dopa/benserazide (50/12.5 mg).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">KW-6002 administered alone produced a dose-dependent antiparkinsonian response that reached the level of efficacy of L-dopa/benserazide but was less likely to reproduce dyskinesias in these animals. When co-administered, KW-6002 potentiated the effects of L-dopa/benserazide on motor activity (up to 30%) without affecting the dyskinetic response.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Adenosine A2A receptor antagonists have antiparkinsonian effects of their own with a reduced propensity to elicit dyskinesias. They might therefore be useful agents in the treatment of PD.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Grondin</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Neuroscience Research Unit, Laval University Research Center, Quebec, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bédard</LastName><ForeName>P J</ForeName><Initials>PJ</Initials></Author><Author ValidYN="Y"><LastName>Hadj Tahar</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Grégoire</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Mori</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Kase</LastName><ForeName>H</ForeName><Initials>H</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Neurology</MedlineTA><NlmUniqueID>0401060</NlmUniqueID><ISSNLinking>0028-3878</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D058915">Purinergic P1 Receptor Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011687">Purines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D043705">Receptor, Adenosine A2A</NameOfSubstance></Chemical><Chemical><RegistryNumber>2GZ0LIK7T4</RegistryNumber><NameOfSubstance UI="C111599">istradefylline</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>9P21XSP91P</RegistryNumber><NameOfSubstance UI="D015632">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015632" MajorTopicYN="N">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008124" MajorTopicYN="N">Locomotion</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008252" MajorTopicYN="N">Macaca fascicularis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010302" MajorTopicYN="N">Parkinson Disease, Secondary</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058915" MajorTopicYN="Y">Purinergic P1 Receptor Antagonists</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011687" MajorTopicYN="N">Purines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043705" MajorTopicYN="N">Receptor, Adenosine A2A</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1999</Year><Month>5</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1999</Year><Month>5</Month><Day>20</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1999</Year><Month>5</Month><Day>20</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10331698</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P J" last="Bédard">P J Bédard</name><name sortKey="Gregoire, L" sort="Gregoire, L" uniqKey="Gregoire L" first="L" last="Grégoire">L. Grégoire</name><name sortKey="Hadj Tahar, A" sort="Hadj Tahar, A" uniqKey="Hadj Tahar A" first="A" last="Hadj Tahar">A. Hadj Tahar</name><name sortKey="Kase, H" sort="Kase, H" uniqKey="Kase H" first="H" last="Kase">H. Kase</name><name sortKey="Mori, A" sort="Mori, A" uniqKey="Mori A" first="A" last="Mori">A. Mori</name></noCountry><country name="Canada"><noRegion><name sortKey="Grondin, R" sort="Grondin, R" uniqKey="Grondin R" first="R" last="Grondin">R. Grondin</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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