The α₂ adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates.
Identifieur interne : 002E52 ( Ncbi/Merge ); précédent : 002E51; suivant : 002E53The α₂ adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates.
Auteurs : Tom H. Johnston [Canada] ; Susan H. Fox ; Matthew J. Piggott ; Juha-Matti Savola ; Jonathan M. BrotchieSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2010.
English descriptors
- KwdEn :
- Adrenergic alpha-2 Receptor Antagonists (pharmacology), Adrenergic alpha-2 Receptor Antagonists (therapeutic use), Analysis of Variance, Animals, Disability Evaluation, Disease Models, Animal, Dopamine Agents (adverse effects), Dopamine Agents (pharmacology), Dopamine Agents (therapeutic use), Drug Therapy, Combination (methods), Dyskinesia, Drug-Induced (drug therapy), Dyskinesia, Drug-Induced (etiology), Female, Imidazoles (pharmacology), Imidazoles (therapeutic use), Indans (pharmacology), Indans (therapeutic use), Levodopa (adverse effects), Levodopa (pharmacology), Levodopa (therapeutic use), Macaca fascicularis, Male, Motor Activity (drug effects), Parkinsonian Disorders (drug therapy), Time Factors.
- MESH :
- chemical , adverse effects : Dopamine Agents, Levodopa.
- chemical , pharmacology : Adrenergic alpha-2 Receptor Antagonists, Dopamine Agents, Imidazoles, Indans, Levodopa.
- chemical , therapeutic use : Adrenergic alpha-2 Receptor Antagonists, Dopamine Agents, Imidazoles, Indans, Levodopa.
- drug effects : Motor Activity.
- drug therapy : Dyskinesia, Drug-Induced, Parkinsonian Disorders.
- etiology : Dyskinesia, Drug-Induced.
- methods : Drug Therapy, Combination.
- Analysis of Variance, Animals, Disability Evaluation, Disease Models, Animal, Female, Macaca fascicularis, Male, Time Factors.
Abstract
Reduction in the antiparkinsonian benefit of levodopa is a major complication of long-term levodopa treatment in advanced Parkinson's disease (PD). Such loss of benefit arises because of reduced duration of action and appearance of disabling dyskinesia. We assess the potential of the α(2) adrenergic antagonist fipamezole to reduce motor complications in parkinsonian macaques. MPTP-lesioned macaques were treated acutely with fipamezole (10 mg/kg) alone and in combination with two doses of levodopa. Fipamezole extended both duration and quality of antiparkinsonian action of levodopa. Duration of antiparkinsonian action, on time, was increased by up to 75% while "good-quality" on time, i.e., that not associated with disabling dyskinesia, was increased by up to 98%. Combination of fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at least equivalent to that provided by the higher dose levodopa alone. However, with the combination, antiparkinsonian benefit was of much better quality. The proportion of on time without disabling dyskinesia (79%) was significantly greater than that with high dose levodopa alone (45%). Increased duration and quality of levodopa action may represent therapeutically valuable actions of α(2) adrenergic antagonists.
DOI: 10.1002/mds.23172
PubMed: 20824735
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Fox</name></author><author><name sortKey="Piggott, Matthew J" sort="Piggott, Matthew J" uniqKey="Piggott M" first="Matthew J" last="Piggott">Matthew J. Piggott</name></author><author><name sortKey="Savola, Juha Matti" sort="Savola, Juha Matti" uniqKey="Savola J" first="Juha-Matti" last="Savola">Juha-Matti Savola</name></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. 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Piggott</name></author><author><name sortKey="Savola, Juha Matti" sort="Savola, Juha Matti" uniqKey="Savola J" first="Juha-Matti" last="Savola">Juha-Matti Savola</name></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. 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Such loss of benefit arises because of reduced duration of action and appearance of disabling dyskinesia. We assess the potential of the α(2) adrenergic antagonist fipamezole to reduce motor complications in parkinsonian macaques. MPTP-lesioned macaques were treated acutely with fipamezole (10 mg/kg) alone and in combination with two doses of levodopa. Fipamezole extended both duration and quality of antiparkinsonian action of levodopa. Duration of antiparkinsonian action, on time, was increased by up to 75% while "good-quality" on time, i.e., that not associated with disabling dyskinesia, was increased by up to 98%. Combination of fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at least equivalent to that provided by the higher dose levodopa alone. However, with the combination, antiparkinsonian benefit was of much better quality. The proportion of on time without disabling dyskinesia (79%) was significantly greater than that with high dose levodopa alone (45%). Increased duration and quality of levodopa action may represent therapeutically valuable actions of α(2) adrenergic antagonists.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">20824735</PMID><DateCreated><Year>2010</Year><Month>10</Month><Day>08</Day></DateCreated><DateCompleted><Year>2011</Year><Month>01</Month><Day>26</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>13</Issue><PubDate><Year>2010</Year><Month>Oct</Month><Day>15</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. 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Duration of antiparkinsonian action, on time, was increased by up to 75% while "good-quality" on time, i.e., that not associated with disabling dyskinesia, was increased by up to 98%. Combination of fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at least equivalent to that provided by the higher dose levodopa alone. However, with the combination, antiparkinsonian benefit was of much better quality. The proportion of on time without disabling dyskinesia (79%) was significantly greater than that with high dose levodopa alone (45%). 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M</ForeName><Initials>JM</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>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D058669">Adrenergic alpha-2 Receptor Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015259">Dopamine Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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UI="D007093">Imidazoles</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007189">Indans</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007980">Levodopa</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000494">pharmacology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008252">Macaca fascicularis</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009043">Motor Activity</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D020734">Parkinsonian Disorders</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000188">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013997">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>9</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>9</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>1</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.23172</ArticleId><ArticleId IdType="pubmed">20824735</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name><name sortKey="Piggott, Matthew J" sort="Piggott, Matthew J" uniqKey="Piggott M" first="Matthew J" last="Piggott">Matthew J. Piggott</name><name sortKey="Savola, Juha Matti" sort="Savola, Juha Matti" uniqKey="Savola J" first="Juha-Matti" last="Savola">Juha-Matti Savola</name></noCountry><country name="Canada"><noRegion><name sortKey="Johnston, Tom H" sort="Johnston, Tom H" uniqKey="Johnston T" first="Tom H" last="Johnston">Tom H. Johnston</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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