PHARMACOLOGICAL CHARACTERIZATION OF MCCG AND MAP4 AT THE MGLUR1B, MGLUR2 AND MGLUR4A HUMAN METABOTROPIC GLUTAMATE-RECEPTOR SUBTYPES

The two reported metabotropic glutamate receptor (mGluR) antagonists, alpha-methyl-cyclopropyl glycine (MCCG) and alpha-methyl-aminophosphonobutyrate (MAP4) were tested on the mGluR1b, mGluR2 and mGluR4a subtypes of human mGluRs. Neither MCCG (500 mu M) nor MAP4 (500 mu M) antagonized the activation of mGluR1b by 10 mu M quisqualate. MCCG was found to potently antagonize the action of 30 mu M (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] at mGluR2 (IC50 = 87.5 mu M; apparent K-D = 25 mu M) but did not block the action of 1 mu M S-2-amino-4-phosphonobutyric acid at mGluR4a (IC50 >> 1 mM). MAP4 was found to be a weak antagonist or partial agonist at mGluR4a (IC50 > 500 mu M) and, less potently, also antagonized the action of 30 mu M (1S,3R)-ACPD) at mGluR2 (IC50 similar to 2 mM).