ParkinsonCanadaV1, Main, Exploration, bibRecord, 003596

Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys

Identifieur interne : 003596 ( Main/Exploration ); précédent : 003595; suivant : 003597

Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys

Auteurs : ABDALLAH HADJ TAHAR [Canada] ; N. Belanger [Canada] ; E. Bangassoro [Canada] ; L. Gregoire [Canada] ; P. J. Bedard [Canada]

Source :

European journal of pharmacology [ 0014-2999 ] ; 2000.

RBID : Pascal:00-0360584

Descripteurs français

Pascal (Inist)
- Parkinson maladie, Clozapine, Analogue, Dyskinésie, Récepteur dopaminergique D4, Antagoniste, Voie souscutanée, Relation dose réponse, Animal, Singe, Traitement, Chimiothérapie, Locomotion, Activité biologique, Antiparkinsonien, JL 18, Dibenzodiazépine.
Wicri :
- topic : Singe.

English descriptors

KwdEn :
- Analog, Animal, Antagonist, Antiparkinson agent, Biological activity, Chemotherapy, Clozapine, D4 Dopamine receptor, Dose activity relation, Dyskinesia, Locomotion, Monkey, Parkinson disease, Subcutaneous administration, Treatment.

Abstract

Clozapine reduces L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesias in parkinsonian patients. To test if the antidyskinetic effect of clozapine is related to antagonism at the dopamine D₄ receptor, we investigated the effect of 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,4]]benzodiazepine (JL-18), a structural analog of clozapine which is more selective for this receptor. Four 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa were used in this study. They were injected subcutaneously (s.c.) with L-Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3, or 0.9 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as control. L-Dopa/benserazide increased locomotion and improved parkinsonism but also induced dyskinesias. Co-administration of JL-18, at low doses (0.1, 0.3 mg/kg) with L-Dopa/benserazide, produced a dose-dependent reduction in L-Dopa-induced dyskinesias without a parallel return to parkinsonism. The present results suggest that novel selective dopamine D₄ receptor antagonists may represent a useful tool to reduce L-Dopa-induced dyskinesias.

Affiliations:

Canada

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Clozapine reduces L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesias in parkinsonian patients. To test if the antidyskinetic effect of clozapine is related to antagonism at the dopamine D<sub>4</sub>
 receptor, we investigated the effect of 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,4]]benzodiazepine (JL-18), a structural analog of clozapine which is more selective for this receptor. Four 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L-Dopa were used in this study. They were injected subcutaneously (s.c.) with L-Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L-Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3, or 0.9 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as control. L-Dopa/benserazide increased locomotion and improved parkinsonism but also induced dyskinesias. Co-administration of JL-18, at low doses (0.1, 0.3 mg/kg) with L-Dopa/benserazide, produced a dose-dependent reduction in L-Dopa-induced dyskinesias without a parallel return to parkinsonism. The present results suggest that novel selective dopamine D<sub>4</sub>
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	La maladie de Parkinson au Canada (serveur d'exploration)
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La maladie de Parkinson au Canada (serveur d'exploration)

Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys

Antidyskinetic effect of JL-18, a clozapine analog, 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