New, potent kainate derivatives: comparison of their affinity for [3H]kainate and [3H]AMPA binding sites.

Newly synthesized kainate derivatives, 4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (HFPA and 4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA), were potent inhibitors of [3H]kainate binding to the rat spinal cord synaptic membranes, comparable in their effectiveness to kainate and domoate, whereas acromelic acid A (ACRO-A) and B (ACRO-B) was much less effective than kainate. ACRO-A, MFPA and HFPA all inhibited [3H]AMPA binding. These novel kainate analogues provide new pharmacological tools for analyzing the mechanisms underlying activation of kainate/AMPA receptors.