A novel selective NMDA agonist, N-phthalamoyl-L-glutamic acid (PhGA)

IONIC currents elicited by N-phthalamoyl-L-glutamic acid (PhGA) were investigated on freshly isolated hippocampal neurons with the whole-cell voltage clamp and concentration clamp techniques. PhGA elicited desensitizing inward currents in Mg-free salines only in the presence of glycine. The dose-response relationship for PhGA was close to a Langmuir isotherm with Kd = 3.7 mM and saturating level 0.75 of that for L-aspartate (L-Asp). PhGA-activated currents were blocked by Mg, D-2-amino-5-phosphonovalerate and kynurenate, and had the same reversal potential as L-Asp-activated currents. Complete cross-desensitization was obtained between the responses to PhGA and L-Asp. We conclude that PhGA is a new selective ‘superacidic’ agonist of the N-methyl-D-aspartate type of glutamate receptor