COMPETITIVE ANTAGONISM AT METABOTROPIC GLUTAMATE RECEPTORS BY (S)-4-CARBOXYPHENYLGLYCINE AND (RS)-ALPHA-METHYL-4-CARBOXYPHENYLGLYCINE

Two phenylglycine derivatives, (S)-4-carboxyphenylglycine and (RS)-alpha-methyl-4-carboxyphenylglycine, competitively antagonised (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD)-stimulated phosphoinositide hydrolysis in rat cerebral cortical slices. The same phenylglycine derivatives selectively antagonized ACPD-induced depolarization in neonatal rat spinal motoneurones and rate thalamic neurones relative to depolarization or excitation induced by N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxY-5-methylisoxazole-4-propionic acid (AMPA). Both phenylglcycine derivatives also selectively depressed synaptic excitation in thalamic neurones evoked by noxious thermal stimuli, without affecting the synaptic stimulation of the same cells by non-noxious stimuli.