(RS)-4-Carboxyphenylglycine

The retention deficit induced by (RS)-alpha-methyl-4-carboxyphenylglycine in a lever-press learning task is blocked by selective agonists of either group I or group II metabotropic glutamate receptors.[Pubmed:10550512]

Exp Brain Res. 1999 Nov;129(1):147-55.

The effects of immediate post-training administration of drugs interacting with group I and/or group II glutamate metabotropic receptors (mGluRs) were determined on the retention performance of a partially acquired lever-press learning task in mice. The antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) dose-dependently (0. 1-100 nmol/mouse, i.c.v.) impairs the retention performance evaluated 24 h post-training. The retention deficit induced by 100 nmol MCPG is related to the selective suppression of a time-dependent spontaneous improvement of performance between the two sessions. This phenomenon appears progressively within 24 h post-training in control mice and is thought to reflect post-training processing of memory traces. The coadministration of either (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), the group I mGluR agonist (R,S)3,5-dihydroxyphenylglycine (DHPG), or the group II mGluR agonist LY354740, completely blocked MCPG-induced deficits at a dose of 0.1 nmol for each agonist. These results suggest that selective activation of either group I or group II mGluRs is able to prevent the memory retention deficits induced by MCPG.

Agonist action of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) in the amygdala.[Pubmed:7632895]

Neuroreport. 1995 May 9;6(7):1058-62.

Glutamatergic excitatory postsynaptic potentials (EPSPs) in the basolateral amygdala (BLA) are reduced in amplitude following agonist activation of presynaptic metabotropic glutamate receptors (mGluR). In this study, the effect of a presumed mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), was investigated on the EPSP recorded intracellularly in BLA neurons. Superfusion of MCPG (500 microM) significantly reduced the amplitude of evoked EPSPs. In the presence of MCPG, postsynaptic responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA, 1 microM) were unaltered while responses to N-methyl-D-aspartate (NMDA, 3-5 microM) were potentiated. These data suggest that the MCPG-induced reduction of EPSP amplitude is due to a mGluR agonist action at a presynaptic mGluR 'autoreceptor'.

(RS)-alpha-Methyl-4-carboxyphenylglycine inhibits long-term potentiation only following the application of low frequency stimulation in the rat dentate gyrus in vitro.[Pubmed:8552300]

Neurosci Lett. 1995 Sep 15;197(3):207-10.

The effect of the metabotropic glutamate receptor (mGluR) antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) was investigated on the induction of long-term potentiation (LTP) of alpha-amino-3-hydroxy-5- methyl-4-isoxazoleproprionate receptor-mediated excitatory postsynaptic currents (epscs) recorded from dentate granule cells in response to presynaptic stimulation of the associational/commissural pathway of the rat dentate gyrus in vitro. MCPG (500 microM, 60 min) did not inhibit the induction of LTP of epscs induced by high frequency stimulation (HFS) at sites which had received only test stimulation (0.05/s) preceding the HFS. MCPG did, however, block the induction of LTP of epscs elicited by HFS if the HFS was preceded by the induction of long-term depression elicited by low frequency stimulation (5 Hz for 3 min). After such low frequency stimulation, HFS induced only a short-term potentiation lasting up to a maximum of 10 min in the presence of MCPG.

Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid).[Pubmed:10096765]

Eur J Pharmacol. 1999 Feb 26;368(1):17-24.

We have studied the effects in three rodent models of generalised convulsive or absence epilepsy of two antagonists of group I metabotropic glutamate receptors that are selective for the mGlu1 receptor. LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid) have been administered intracerebroventricularly (i.c.v.) to DBA/2 mice and lethargic mice (lh/lh), and focally into the inferior colliculus of genetically epilepsy prone rats (GEPR). In DBA/2 mice both compounds produce a rapid, transient suppression of sound-induced clonic seizures (LY 367385: ED50 = 12 nmol, i.c.v., 5 min; AIDA: ED50 = 79 nmol, i.c.v., 15 min). In lethargic mice both compounds significantly reduce the incidence of spontaneous spike and wave discharges on the electroencephalogram, from <30 to >150 min after the administration of AIDA, 500 nmol, i.c.v., and from 30 to >150 min after the administration of LY 367385, 250 nmol, i.c.v. LY 367385, 50 nmol, suppresses spontaneous spike and wave discharges from 30 to 60 min. In genetically epilepsy prone rats both compounds reduce sound-induced clonic seizures. LY 367385, 160 nmol bilaterally, fully suppresses clonic seizures after 2-4 h. AIDA is fully effective 30 min after 100 nmol bilaterally. It is concluded that antagonists of mGlu1 receptors are potential anticonvulsant agents and that activation of mGlu1 receptors probably contributes to a variety of epileptic syndromes.