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.
Kwak
S
S
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Aizawa
H
H
Ishida
M
M
Shinozaki
H
H
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D007608:Kainic Acid; D009467:Neuromuscular Depolarizing Agents; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; C077108:4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid; C074250:4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid