Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia.
Mov Disord.. 2013-02-06; 28(8): 1088-1096
DOI: 10.1002/mds.25366
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1. Mov Disord. 2013 Jul;28(8):1088-96. doi: 10.1002/mds.25366. Epub 2013 Feb 6.
Study of the antidyskinetic effect of eltoprazine in animal models of
levodopa-induced dyskinesia.
Bezard E(1), Tronci E, Pioli EY, Li Q, Porras G, Björklund A, Carta M.
Author information:
(1)Institute for Neurodegenerative Diseases, Bordeaux University, Bordeaux,
France.
The serotonin (5-hydroxytryptamine [5HT]) system has recently emerged as an
important player in the appearance of l-3,4-dihydroxyphenylalanine (levodopa
[l-dopa])-induced dyskinesia in animal models of Parkinson’s disease. In fact,
dopamine released as a false transmitter from serotonin neurons appears to
contribute to the pulsatile stimulation of dopamine receptors, leading to the
appearance of the abnormal involuntary movements. Thus, drugs able to dampen the
activity of serotonin neurons hold promise for the treatment of dyskinesia. The
authors investigated the ability of the mixed 5-HT 1A/1B receptor agonist
eltoprazine to counteract l-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned
rats and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques.
The data demonstrated that eltoprazine is extremely effective in suppressing
dyskinesia in experimental models, although this effect was accompanied by a
partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine
was found to (synergistically) potentiate the antidyskinetic effect of
amantadine. The current data indicated that eltoprazine is highly effective in
counteracting dyskinesia in preclinical models. However, the partial worsening of
the l-dopa effect observed after eltoprazine administration represents a concern;
whether this side effect is due to a limitation of the animal models or to an
intrinsic property of eltoprazine needs to be addressed in ongoing clinical
trials. The data also suggest that the combination of low doses of eltoprazine
with amantadine may represent a valid strategy to increase the antidyskinetic
effect and reduce the eltoprazine-induced worsening of l-dopa therapeutic
effects.
Copyright © 2012 Movement Disorder Society.
DOI: 10.1002/mds.25366
PMID: 23389842 [Indexed for MEDLINE]