A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1610460
- author
- 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
- organization
- publishing date
- 2010
- 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
- pmid:20452425
- 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
- 2016-04-04 08:06:34
- date last changed
- 2024-06-08 02:36:10
@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}}, doi = {{10.1016/j.nbd.2010.05.001}}, volume = {{39}}, year = {{2010}}, }