Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinson's model.

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

Neuroreport

journal_title

Neuroreport

authors

Vernon AC,Croucher MJ,Dexter DT

doi

10.1097/WNR.0b013e3282f602df

subject

Has Abstract

pub_date

2008-03-05 00:00:00

pages

475-8

issue

4

eissn

0959-4965

issn

1473-558X

pii

00001756-200803050-00017

journal_volume

19

pub_type

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