NEW, POTENT KAINATE DERIVATIVES - COMPARISON OF THEIR AFFINITY FOR [H-3] KAINATE AND [H-3] 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 [H-3]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 [H-3]AMPA binding. These novel kainate analogues provide new pharmacological tools for analyzing the mechanisms underlying activation of kainate/AMPA receptors.