Advanced

Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia

Bezard, Erwan; Tronci, Elisabetta LU ; Pioli, Elsa Y.; Li, Qin; Porras, Gregory; Björklund, Anders LU and Carta, Manolo LU (2013) In Movement Disorders 28(8). p.1088-1096
Abstract
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... (More)
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. (c) 2013 Movement Disorder Society (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dyskinesia, levodopa, eltoprazine, serotonin, amantadine
in
Movement Disorders
volume
28
issue
8
pages
1088 - 1096
publisher
John Wiley & Sons
external identifiers
  • wos:000322960800018
  • scopus:84881556666
ISSN
0885-3185
DOI
10.1002/mds.25366
language
English
LU publication?
yes
id
720e313e-726b-44f2-b7bf-7af37953462e (old id 4039636)
date added to LUP
2013-10-01 15:17:43
date last changed
2019-08-07 01:19:29
@article{720e313e-726b-44f2-b7bf-7af37953462e,
  abstract     = {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. (c) 2013 Movement Disorder Society},
  author       = {Bezard, Erwan and Tronci, Elisabetta and Pioli, Elsa Y. and Li, Qin and Porras, Gregory and Björklund, Anders and Carta, Manolo},
  issn         = {0885-3185},
  keyword      = {dyskinesia,levodopa,eltoprazine,serotonin,amantadine},
  language     = {eng},
  number       = {8},
  pages        = {1088--1096},
  publisher    = {John Wiley & Sons},
  series       = {Movement Disorders},
  title        = {Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia},
  url          = {http://dx.doi.org/10.1002/mds.25366},
  volume       = {28},
  year         = {2013},
}