Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia.
Neuroscience Research. 2013-12-01; 77(4): 242-246
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1. Neurosci Res. 2013 Dec;77(4):242-6. doi: 10.1016/j.neures.2013.10.002. Epub 2013
Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced
Bézard E(1), Muñoz A, Tronci E, Pioli EY, Li Q, Porras G, Björklund A, Carta M.
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Institute of Lab Animal Sciences, China Academy of
Medical Sciences, Beijing, China.
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
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PMID: 24135129 [Indexed for MEDLINE]