ParkinsonCanadaV1, Main, Exploration, bibRecord, 003557

Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys

Identifieur interne : 003557 ( Main/Exploration ); précédent : 003556; suivant : 003558

Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys

Auteurs : ABDALLAH HADJ TAHAR [Canada] ; Laurent Gregoire [Canada] ; Evelyne Bangassoro [Canada] ; Paul J. Bedard [Canada]

Source :

Clinical neuropharmacology [ 0362-5664 ] ; 2000.

RBID : Pascal:00-0500117

Descripteurs français

Pascal (Inist)
- Lévodopa, Antiparkinsonien, Parkinson maladie, Dyskinésie, Toxicité, Cabergoline, Stimulant dopaminergique, Récepteur dopaminergique D2, Agoniste, Traitement, Chimiothérapie, Activité biologique, Long terme, Relation dose réponse, Animal, Ergot dérivé, Singe, Voie souscutanée.
Wicri :
- topic : Singe.

English descriptors

KwdEn :
- Agonist, Animal, Antiparkinson agent, Biological activity, Cabergoline, Chemotherapy, D2 Dopamine receptor, Dopamine agonist, Dose activity relation, Dyskinesia, Ergot derivatives, Levodopa, Long term, Monkey, Parkinson disease, Subcutaneous administration, Toxicity, Treatment.

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.

Affiliations:

Canada

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Le document en format XML

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<front><div type="abstract" xml:lang="en">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 D<sub>2</sub>
-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 D<sub>2</sub>
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	La maladie de Parkinson au Canada (serveur d'exploration)
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Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys

Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri