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Journal of Neuroscience, Vol 9, 3230-3236, Copyright © 1989 by Society for Neuroscience
Quantitative physiological characterization of a quinoxalinedione non- NMDA receptor antagonist
KA Yamada, JM Dubinsky and SM Rothman
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
The effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, or FG 9065) on
excitatory amino acid responses in cultured neurons from rat hippocampus
were studied using tight-seal whole-cell recording techniques. CNQX reduced
the magnitude of peak inward currents produced by exogenously applied
kainate, quisqualate, and N-methyl-D-aspartate (NMDA) with Ki's of 2.5,
3.5, and 96 microM, respectively. The antagonism was competitive against
kainate and quisqualate, but noncompetitive against NMDA. Glycine markedly
reduced CNQX antagonism of NMDA responses. The same recording technique
using pairs of monosynaptically connected neurons demonstrated reversible
diminution of excitatory postsynaptic potentials in 7 of 7 pairs, using
CNQX at concentrations as low as 10 microM. CNQX applied alone did not
evoke inward or outward currents at membrane potentials near the resting
membrane potential and did not affect the current-voltage relationship at
membrane potentials between -90 and -30 mV. These observations represent
the first quantitative characterization of glutamate receptor antagonism by
CNQX with respect to physiological rather than biochemical parameters and
demonstrate that CNQX is far more potent and more selective than currently
available non-NMDA antagonists. The results suggest that CNQX will be a
useful pharmacologic tool for the study of synaptic transmission in a
variety of systems in which glutamate or related excitatory amino acids are
involved.
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