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A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys.

Rylander, Daniella LU ; Iderberg, Hanna LU ; Li, Qin; Dekundy, Andrzej; Zhang, Jinlan; Li, Hao; Baishen, Ren; Danysz, Wojciech; Bezard, Erwan and Cenci Nilsson, Angela LU (2010) In Neurobiology of Disease 39. p.352-361
Abstract
L-DOPA remains the gold-standard treatment for Parkinson's disease but causes motor fluctuations and dyskinesia. Metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for antidyskinetic therapies. Here, we evaluate the effects of fenobam, a noncompetitive mGluR5 antagonist already tested in humans, using rodent and nonhuman primate models of L-DOPA-induced dyskinesia. In both animal models, acute administration of fenobam attenuated the L-DOPA-induced abnormal involuntary movements (50-70% reduction at the doses of 30mg/kg in rats and 10mg/kg in monkeys). The effect consisted in a reduction of peak-dose dyskinesia, whereas the end-dose phase was not affected. Chronic administration of fenobam to previously... (More)
L-DOPA remains the gold-standard treatment for Parkinson's disease but causes motor fluctuations and dyskinesia. Metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for antidyskinetic therapies. Here, we evaluate the effects of fenobam, a noncompetitive mGluR5 antagonist already tested in humans, using rodent and nonhuman primate models of L-DOPA-induced dyskinesia. In both animal models, acute administration of fenobam attenuated the L-DOPA-induced abnormal involuntary movements (50-70% reduction at the doses of 30mg/kg in rats and 10mg/kg in monkeys). The effect consisted in a reduction of peak-dose dyskinesia, whereas the end-dose phase was not affected. Chronic administration of fenobam to previously drug-naïve animals (de novo treatment) attenuated the development of peak-dose dyskinesia without compromising the anti-parkinsonian effect of L-DOPA. In addition, fenobam prolonged the motor stimulant effect of L-DOPA. We conclude that fenobam acts similarly in rat and primate models of L-DOPA-induced dyskinesia and that it represents a good candidate for antidyskinetic treatment in Parkinson's disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurobiology of Disease
volume
39
pages
352 - 361
publisher
Elsevier
external identifiers
  • wos:000280544100014
  • pmid:20452425
  • scopus:77954956744
ISSN
0969-9961
DOI
10.1016/j.nbd.2010.05.001
language
English
LU publication?
yes
id
fb69a94b-b565-4bca-a646-245ab770b48e (old id 1610460)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20452425?dopt=Abstract
date added to LUP
2010-06-01 09:56:21
date last changed
2018-06-10 04:49:05
@article{fb69a94b-b565-4bca-a646-245ab770b48e,
  abstract     = {L-DOPA remains the gold-standard treatment for Parkinson's disease but causes motor fluctuations and dyskinesia. Metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for antidyskinetic therapies. Here, we evaluate the effects of fenobam, a noncompetitive mGluR5 antagonist already tested in humans, using rodent and nonhuman primate models of L-DOPA-induced dyskinesia. In both animal models, acute administration of fenobam attenuated the L-DOPA-induced abnormal involuntary movements (50-70% reduction at the doses of 30mg/kg in rats and 10mg/kg in monkeys). The effect consisted in a reduction of peak-dose dyskinesia, whereas the end-dose phase was not affected. Chronic administration of fenobam to previously drug-naïve animals (de novo treatment) attenuated the development of peak-dose dyskinesia without compromising the anti-parkinsonian effect of L-DOPA. In addition, fenobam prolonged the motor stimulant effect of L-DOPA. We conclude that fenobam acts similarly in rat and primate models of L-DOPA-induced dyskinesia and that it represents a good candidate for antidyskinetic treatment in Parkinson's disease.},
  author       = {Rylander, Daniella and Iderberg, Hanna and Li, Qin and Dekundy, Andrzej and Zhang, Jinlan and Li, Hao and Baishen, Ren and Danysz, Wojciech and Bezard, Erwan and Cenci Nilsson, Angela},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {352--361},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2010.05.001},
  volume       = {39},
  year         = {2010},
}