Analogs of a superacidic NMDA receptor agonist, N-phthalamoyl-L-glutamic acid (PhGA): Activity and mode of interaction with the receptor recognition site

Studies of the effects of analogs of N-phthalamoyl-L-glutamic acid (PhGA, experiments on freshly isolated hippocampal neurons of rats and on mice using intracerebroventricular injection) were compared with the molecular modeling studies. Transmembrane currents evoked by applications of NMDA receptor agonists were recorded using a patch-clamp technique. Interaction of PhGA derivatives with the NMDA receptors was examined by comparing their agonistic activity with that of L-aspartate. It was found that the derivatives (iso- and tere-PhGA), which contain three carboxylic groups, display a strong agonistic activity. The absence of carboxylic groups in the molecule of an agonist and lengthening of the methylene chain in the aliphatic part of the molecule result in a drop in agonistic activity.