Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys.
Identifieur interne : 001633 ( PubMed/Curation ); précédent : 001632; suivant : 001634Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys.
Auteurs : A. Hadj Tahar [Canada] ; L. Grégoire ; E. Bangassoro ; P J BédardSource :
- Clinical neuropharmacology [ 0362-5664 ]
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (antagonists & inhibitors), Antiparkinson Agents (therapeutic use), Antiparkinson Agents (toxicity), Behavior, Animal (drug effects), Benserazide (pharmacology), Dyskinesia, Drug-Induced (drug therapy), Ergolines (therapeutic use), Female, Levodopa (antagonists & inhibitors), Levodopa (toxicity), Macaca fascicularis, Motor Activity (drug effects), Parkinson Disease, Secondary (complications), Receptors, Dopamine D2 (drug effects).
- MESH :
- chemical , antagonists & inhibitors : Antiparkinson Agents, Levodopa.
- chemical , drug effects : Receptors, Dopamine D2.
- chemical , pharmacology : Benserazide.
- chemical , therapeutic use : Antiparkinson Agents, Ergolines.
- chemical , toxicity : Antiparkinson Agents, Levodopa.
- complications : Parkinson Disease, Secondary.
- drug effects : Behavior, Animal, Motor Activity.
- drug therapy : Dyskinesia, Drug-Induced.
- Animals, Female, Macaca fascicularis.
Abstract
The pathophysiology of L-Dopa-induced dyskinesias (LID), a common problem after long-term use of L-dopa in the treatment of Parkinson's disease (PD), is not completely understood. Oscillations in L-Dopa concentrations in the brain are believed to be responsible, at least in part, for their pathogenesis. This study was aimed at verifying whether chronic administration of cabergoline, a long-acting dopamine D2-like receptor agonist, can reverse established LID. Four MPTP-treated cynomolgus monkeys with long-standing and stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa, were used in this study. We compared the antiparkinsonian and dyskinetic responses of L-Dopa methyl ester (62.5 mg and 125 mg), given with benserazide (50 mg) (L-Dopa/benserazide), administered before and after a 6-week period during which the animals were treated only by daily administration of cabergoline (doses ranging from 0.125 to 0.185 mg/kg, subcutaneous). During cabergoline treatment, the monkeys initially showed marked dyskinesias, which were reduced significantly after 4 weeks of treatment. However, there was no tolerance to its antiparkinsonian effect. L-Dopa/benserazide given 4 days after cabergoline withdrawal produced a significant antiparkinsonian effect, but dyskinesias were dramatically reduced compared to what had been seen before chronic cabergoline treatment. The duration of the L-Dopa response was not increased after chronic administration of cabergoline. Our data suggest that sustained dopamine D2 receptor stimulation could be of value when trying to reduce or to reverse LID in patients with fluctuating advanced PD.
PubMed: 11020123
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Bangassoro</name></author><author><name sortKey="Bedard, P J" sort="Bedard, P J" uniqKey="Bedard P" first="P J" last="Bédard">P J Bédard</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="????"><PubDate><MedlineDate>2000 Jul-Aug</MedlineDate></PubDate></date><idno type="RBID">pubmed:11020123</idno><idno type="pmid">11020123</idno><idno type="wicri:Area/PubMed/Corpus">001633</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001633</idno><idno type="wicri:Area/PubMed/Curation">001633</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001633</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys.</title><author><name sortKey="Hadj Tahar, A" sort="Hadj Tahar, A" uniqKey="Hadj Tahar A" first="A" last="Hadj Tahar">A. 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Oscillations in L-Dopa concentrations in the brain are believed to be responsible, at least in part, for their pathogenesis. This study was aimed at verifying whether chronic administration of cabergoline, a long-acting dopamine D2-like receptor agonist, can reverse established LID. Four MPTP-treated cynomolgus monkeys with long-standing and stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa, were used in this study. We compared the antiparkinsonian and dyskinetic responses of L-Dopa methyl ester (62.5 mg and 125 mg), given with benserazide (50 mg) (L-Dopa/benserazide), administered before and after a 6-week period during which the animals were treated only by daily administration of cabergoline (doses ranging from 0.125 to 0.185 mg/kg, subcutaneous). During cabergoline treatment, the monkeys initially showed marked dyskinesias, which were reduced significantly after 4 weeks of treatment. However, there was no tolerance to its antiparkinsonian effect. L-Dopa/benserazide given 4 days after cabergoline withdrawal produced a significant antiparkinsonian effect, but dyskinesias were dramatically reduced compared to what had been seen before chronic cabergoline treatment. The duration of the L-Dopa response was not increased after chronic administration of cabergoline. Our data suggest that sustained dopamine D2 receptor stimulation could be of value when trying to reduce or to reverse LID in patients with fluctuating advanced PD.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11020123</PMID><DateCreated><Year>2001</Year><Month>02</Month><Day>02</Day></DateCreated><DateCompleted><Year>2001</Year><Month>02</Month><Day>02</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0362-5664</ISSN><JournalIssue CitedMedium="Print"><Volume>23</Volume><Issue>4</Issue><PubDate><MedlineDate>2000 Jul-Aug</MedlineDate></PubDate></JournalIssue><Title>Clinical neuropharmacology</Title><ISOAbbreviation>Clin Neuropharmacol</ISOAbbreviation></Journal><ArticleTitle>Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys.</ArticleTitle><Pagination><MedlinePgn>195-202</MedlinePgn></Pagination><Abstract><AbstractText>The pathophysiology of L-Dopa-induced dyskinesias (LID), a common problem after long-term use of L-dopa in the treatment of Parkinson's disease (PD), is not completely understood. Oscillations in L-Dopa concentrations in the brain are believed to be responsible, at least in part, for their pathogenesis. This study was aimed at verifying whether chronic administration of cabergoline, a long-acting dopamine D2-like receptor agonist, can reverse established LID. Four MPTP-treated cynomolgus monkeys with long-standing and stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa, were used in this study. We compared the antiparkinsonian and dyskinetic responses of L-Dopa methyl ester (62.5 mg and 125 mg), given with benserazide (50 mg) (L-Dopa/benserazide), administered before and after a 6-week period during which the animals were treated only by daily administration of cabergoline (doses ranging from 0.125 to 0.185 mg/kg, subcutaneous). During cabergoline treatment, the monkeys initially showed marked dyskinesias, which were reduced significantly after 4 weeks of treatment. However, there was no tolerance to its antiparkinsonian effect. L-Dopa/benserazide given 4 days after cabergoline withdrawal produced a significant antiparkinsonian effect, but dyskinesias were dramatically reduced compared to what had been seen before chronic cabergoline treatment. The duration of the L-Dopa response was not increased after chronic administration of cabergoline. 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