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6-Cyano-7-nitroquinoxaline-2,3-dione as an excitatory amino acid antagonist in area CA1 of rat hippocampus.
Br J Pharmacol. 1989 May; 97(1):71-6.BJ

Abstract

1. A quantitative pharmacological investigation of the excitatory amino acid antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) has been made in area CA1 of rat hippocampal slices bathed in 1 mM Mg2+ containing medium. 2. At a concentration of 10 microM, CNQX reversibly antagonized responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualate and kainate; it produced a parallel shift in their log dose-response curves. Responses to N-methyl-D-aspartate (NMDA) were not antagonized by 10 microM CNQX (dose-ratio: 1.04 +/- 0.06, n = 3). 3. Schild plots (constructed over the range 1-100 microM) yielded the following estimated pA2 values, AMPA 5.8, quisqualate 5.9, and kainate 5.9. NMDA was antagonized by 100 microM CNQX, giving an apparent log K of 4.44 +/- 0.06. 4. The slopes (+/- s.e. mean) of the Schild plots were for AMPA 0.84 +/- 0.06, quisqualate 0.79 +/- 0.04 and kainate 0.68 +/- 0.07. These were all significantly less than unity. 5. Synaptic responses elicited by low frequency activation of the Schaffer collateral-commissural pathway were blocked completely by CNQX (10 microM) providing that a low stimulus intensity was used. With high intensity stimulation a small component remained that was blocked by the selective NMDA antagonist D-2-amino-5-phosphonovalerate (APV). 6. These results suggest that CNQX does not differentially affect the responses of CA1 neurones to AMPA, quisqualate and kainate. It does, however, depress responses to these agonists to a greater degree than it does responses to NMDA and it is a highly effective synaptic antagonist.

Authors+Show Affiliations

Department of Anatomy, School of Medical Sciences, University of Bristol.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2566354

Citation

Blake, J F., et al. "6-Cyano-7-nitroquinoxaline-2,3-dione as an Excitatory Amino Acid Antagonist in Area CA1 of Rat Hippocampus." British Journal of Pharmacology, vol. 97, no. 1, 1989, pp. 71-6.
Blake JF, Yates RG, Brown MW, et al. 6-Cyano-7-nitroquinoxaline-2,3-dione as an excitatory amino acid antagonist in area CA1 of rat hippocampus. Br J Pharmacol. 1989;97(1):71-6.
Blake, J. F., Yates, R. G., Brown, M. W., & Collingridge, G. L. (1989). 6-Cyano-7-nitroquinoxaline-2,3-dione as an excitatory amino acid antagonist in area CA1 of rat hippocampus. British Journal of Pharmacology, 97(1), 71-6.
Blake JF, et al. 6-Cyano-7-nitroquinoxaline-2,3-dione as an Excitatory Amino Acid Antagonist in Area CA1 of Rat Hippocampus. Br J Pharmacol. 1989;97(1):71-6. PubMed PMID: 2566354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 6-Cyano-7-nitroquinoxaline-2,3-dione as an excitatory amino acid antagonist in area CA1 of rat hippocampus. AU - Blake,J F, AU - Yates,R G, AU - Brown,M W, AU - Collingridge,G L, PY - 1989/5/1/pubmed PY - 1989/5/1/medline PY - 1989/5/1/entrez SP - 71 EP - 6 JF - British journal of pharmacology JO - Br J Pharmacol VL - 97 IS - 1 N2 - 1. A quantitative pharmacological investigation of the excitatory amino acid antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) has been made in area CA1 of rat hippocampal slices bathed in 1 mM Mg2+ containing medium. 2. At a concentration of 10 microM, CNQX reversibly antagonized responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualate and kainate; it produced a parallel shift in their log dose-response curves. Responses to N-methyl-D-aspartate (NMDA) were not antagonized by 10 microM CNQX (dose-ratio: 1.04 +/- 0.06, n = 3). 3. Schild plots (constructed over the range 1-100 microM) yielded the following estimated pA2 values, AMPA 5.8, quisqualate 5.9, and kainate 5.9. NMDA was antagonized by 100 microM CNQX, giving an apparent log K of 4.44 +/- 0.06. 4. The slopes (+/- s.e. mean) of the Schild plots were for AMPA 0.84 +/- 0.06, quisqualate 0.79 +/- 0.04 and kainate 0.68 +/- 0.07. These were all significantly less than unity. 5. Synaptic responses elicited by low frequency activation of the Schaffer collateral-commissural pathway were blocked completely by CNQX (10 microM) providing that a low stimulus intensity was used. With high intensity stimulation a small component remained that was blocked by the selective NMDA antagonist D-2-amino-5-phosphonovalerate (APV). 6. These results suggest that CNQX does not differentially affect the responses of CA1 neurones to AMPA, quisqualate and kainate. It does, however, depress responses to these agonists to a greater degree than it does responses to NMDA and it is a highly effective synaptic antagonist. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/2566354/6_Cyano_7_nitroquinoxaline_23_dione_as_an_excitatory_amino_acid_antagonist_in_area_CA1_of_rat_hippocampus_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-1188&date=1989&volume=97&issue=1&spage=71 DB - PRIME DP - Unbound Medicine ER -