Inhibition of group I metabotropic glutamate receptor responses in vivo in rats by a new generation of carboxyphenylglycine-like amino acid antagonists.
Neurosci Lett
; 330(2): 127-30, 2002 Sep 20.
Article
in En
| MEDLINE
| ID: mdl-12231428
ABSTRACT
A series of novel group I metabotropic glutamate receptor (mGlu) antagonists have been designed on the basis of the 4-carboxyphenylglycine pharmacophore. The compounds are either mGlu1 receptor selective or equipotent for both mGlu1 and mGlu5 receptors and have IC(50) values ranging from 1 to 30 microM determined by phosphoinositide hydrolysis (PI) assay in vitro. All the compounds produced dose-dependent inhibition of group I mGlu receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG)-induced limbic seizure responses in mice with ED(50) values ranging from 9 nmol for LY393053 to 138 nmol for LY339840 after intracerebroventricular injection and were more potent than the mGlu1 receptor antagonist 1-aminoindan-1,5-dicarboxylic acid (ED(50)=477 nmol). Further antagonist actions were also demonstrated in a model of (RS)-DHPG-induced PI hydrolysis in vivo such that LY367385 and the active cis isomer of LY393053 produced dose-dependent inhibition of PI responses in both cerebellum and hippocampus. Cis LY393053 also inhibited hippocampal PI responses when administered intraperitoneally at a dose of 30 mg/kg. These compounds define a new series of group I mGlu receptor antagonists which may serve as useful experimental tools.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzoates
/
Receptors, Metabotropic Glutamate
/
Excitatory Amino Acid Antagonists
/
Glycine
Limits:
Animals
Language:
En
Journal:
Neurosci Lett
Year:
2002
Document type:
Article
Affiliation country:
United States