Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia.
Identifieur interne : 000662 ( PubMed/Corpus ); précédent : 000661; suivant : 000663Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia.
Auteurs : Erwan Bézard ; Ana Mu Oz ; Elisabetta Tronci ; Elsa Y. Pioli ; Qin Li ; Gregory Porras ; Anders Björklund ; Manolo CartaSource :
- Neuroscience research [ 1872-8111 ] ; 2013.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (adverse effects), Dyskinesia, Drug-Induced (drug therapy), Female, Levodopa (adverse effects), Macaca fascicularis, Parkinsonian Disorders (drug therapy), Piperidines (therapeutic use), Pyridines (therapeutic use), Rats, Rats, Sprague-Dawley, Serotonin 5-HT1 Receptor Agonists (therapeutic use).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- drug therapy : Dyskinesia, Drug-Induced, Parkinsonian Disorders.
- chemical , therapeutic use : Piperidines, Pyridines, Serotonin 5-HT1 Receptor Agonists.
- Animals, Female, Macaca fascicularis, Rats, Rats, Sprague-Dawley.
Abstract
The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract L-DOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0mg/kg). At a lower dose (0.75mg/kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease.
DOI: 10.1016/j.neures.2013.10.002
PubMed: 24135129
Links to Exploration step
pubmed:24135129Le document en format XML
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<author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name>
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<author><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name>
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<front><div type="abstract" xml:lang="en">The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract L-DOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0mg/kg). At a lower dose (0.75mg/kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease.</div>
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<Abstract><AbstractText>The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract L-DOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0mg/kg). At a lower dose (0.75mg/kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease.</AbstractText>
<CopyrightInformation>Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.</CopyrightInformation>
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