Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats.
Identifieur interne : 002D80 ( PubMed/Curation ); précédent : 002D79; suivant : 002D81Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats.
Auteurs : Concepci Marin [Espagne] ; Esther Aguilar ; José A. ObesoSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2006.
English descriptors
- KwdEn :
- Analysis of Variance, Animals, Antiparkinson Agents (therapeutic use), Catechols (therapeutic use), Disease Models, Animal, Drug Therapy, Combination, Dyskinesias (drug therapy), Dyskinesias (etiology), Levodopa (therapeutic use), Male, Nitriles, Oxidopamine (toxicity), Parkinsonian Disorders (chemically induced), Parkinsonian Disorders (complications), Parkinsonian Disorders (drug therapy), Rats, Rats, Sprague-Dawley, Severity of Illness Index, Time Factors.
- MESH :
- chemical , therapeutic use : Antiparkinson Agents, Catechols, Levodopa.
- chemically induced : Parkinsonian Disorders.
- complications : Parkinsonian Disorders.
- drug therapy : Dyskinesias, Parkinsonian Disorders.
- etiology : Dyskinesias.
- chemical , toxicity : Oxidopamine.
- Analysis of Variance, Animals, Disease Models, Animal, Drug Therapy, Combination, Male, Nitriles, Rats, Rats, Sprague-Dawley, Severity of Illness Index, Time Factors.
Abstract
Levodopa-induced dyskinesias (LIDs) have been associated with a sequence of events that includes pulsatile stimulation of dopamine receptors. The degree of nigrostriatal degeneration, the half-life of dopaminomimetic agents, and the dose of levodopa used to treat parkinsonian symptoms are factors directly correlated with the development of motor complications in Parkinson's disease patients. Long-acting agents producing continuous dopaminergic stimulation are less likely to prime for dyskinesia than short-acting drugs that produce pulsatile stimulation of dopamine receptors. Inhibition of the enzyme catechol-O-methyl transferase (COMT) by entacapone extends the half-life of levodopa and minimizes variability in plasma levodopa levels. The aim of the present study was to characterize the effect of the early administration of the COMT inhibitor entacapone in the recently described model of LIDs in rats with a nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. Animals were treated either with levodopa (6 mg/kg, twice at day, i.p.) plus entacapone (30 mg/kg per day, i.p.) or levodopa (6 mg/kg, twice at day, i.p.) plus vehicle for 22 consecutive days. Early administration of entacapone, in association with levodopa, induces a decrease in the severity of dyskinesia and delays their onset in hemiparkinsonian rats. All dyskinesia subtypes evaluated, such as axial, limb, and orofacial dyskinesias, have shown similar reductions. These results suggest that entacapone, by extending levodopa elimination half-life, might reduce its propensity to induce motor complications.
DOI: 10.1002/mds.20780
PubMed: 16437585
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Obeso</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="doi">10.1002/mds.20780</idno><idno type="RBID">pubmed:16437585</idno><idno type="pmid">16437585</idno><idno type="wicri:Area/PubMed/Corpus">002D80</idno><idno type="wicri:Area/PubMed/Curation">002D80</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats.</title><author><name sortKey="Marin, Concepci" sort="Marin, Concepci" uniqKey="Marin C" first="Concepci" last="Marin">Concepci Marin</name><affiliation wicri:level="1"><nlm:affiliation>Laboratori de Neurologia Experimental, Fundació Clínic-Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain. cmarin@clinic.ub.es</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Laboratori de Neurologia Experimental, Fundació Clínic-Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Aguilar, Esther" sort="Aguilar, Esther" uniqKey="Aguilar E" first="Esther" last="Aguilar">Esther Aguilar</name></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="José A" last="Obeso">José A. 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The degree of nigrostriatal degeneration, the half-life of dopaminomimetic agents, and the dose of levodopa used to treat parkinsonian symptoms are factors directly correlated with the development of motor complications in Parkinson's disease patients. Long-acting agents producing continuous dopaminergic stimulation are less likely to prime for dyskinesia than short-acting drugs that produce pulsatile stimulation of dopamine receptors. Inhibition of the enzyme catechol-O-methyl transferase (COMT) by entacapone extends the half-life of levodopa and minimizes variability in plasma levodopa levels. The aim of the present study was to characterize the effect of the early administration of the COMT inhibitor entacapone in the recently described model of LIDs in rats with a nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. Animals were treated either with levodopa (6 mg/kg, twice at day, i.p.) plus entacapone (30 mg/kg per day, i.p.) or levodopa (6 mg/kg, twice at day, i.p.) plus vehicle for 22 consecutive days. Early administration of entacapone, in association with levodopa, induces a decrease in the severity of dyskinesia and delays their onset in hemiparkinsonian rats. All dyskinesia subtypes evaluated, such as axial, limb, and orofacial dyskinesias, have shown similar reductions. These results suggest that entacapone, by extending levodopa elimination half-life, might reduce its propensity to induce motor complications.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">16437585</PMID><DateCreated><Year>2006</Year><Month>05</Month><Day>11</Day></DateCreated><DateCompleted><Year>2006</Year><Month>10</Month><Day>18</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>21</Volume><Issue>5</Issue><PubDate><Year>2006</Year><Month>May</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. 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The aim of the present study was to characterize the effect of the early administration of the COMT inhibitor entacapone in the recently described model of LIDs in rats with a nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. Animals were treated either with levodopa (6 mg/kg, twice at day, i.p.) plus entacapone (30 mg/kg per day, i.p.) or levodopa (6 mg/kg, twice at day, i.p.) plus vehicle for 22 consecutive days. Early administration of entacapone, in association with levodopa, induces a decrease in the severity of dyskinesia and delays their onset in hemiparkinsonian rats. All dyskinesia subtypes evaluated, such as axial, limb, and orofacial dyskinesias, have shown similar reductions. 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