Abstract:
:Pharmacological activation of group III metabotropic glutamate receptors (mGluR) or inhibition of group I mGluR by subtype-selective ligands is neuroprotective in experimental models of Parkinson's disease. The aim of this study was to investigate whether targeting both receptor subtypes simultaneously produces enhanced neuroprotection. Rodents bearing a 6-hydroxydopamine lesion were intranigrally administered either the group III mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid or the group I mGluR antagonist 2-methyl-6-(phenylethynyl)pyridine, alone or in combination. Coadministration of L-(+)-2-amino-4-phosphonobutyric acid and 2-methyl-6-(phenylethynyl)pyridine resulted in robust nigrostriatal neuroprotection that was significantly increased compared with either compound alone. These data suggest that targeting multiple mGluR subtypes with low doses of selective ligands may provide an enhanced therapeutic response in experimental models of Parkinson's disease.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Vernon AC,Croucher MJ,Dexter DTdoi
10.1097/WNR.0b013e3282f602dfsubject
Has Abstractpub_date
2008-03-05 00:00:00pages
475-8issue
4eissn
0959-4965issn
1473-558Xpii
00001756-200803050-00017journal_volume
19pub_type
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