6,7-Dinitroquinoxaline-2,3-dione and 6-nitro,7-cyanoquinoxaline-2,3-dione antagonize responses mediated by N-methyl-d-aspartate and NMDA-associated glycine recognition sites in vivo: Measurements of cerebellar cyclic-GMP

T. S. Rao, J. A. Cler, S. J. Mick, M. R. Emmett, S. Iyengar, P. L. Wood

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Direct intracerebellar administration of quisqualate resulted in marked increases in levels of cGMP in the cerebellum of the mouse, with a Hill number of 2.0. Quinoxalinediones, DNQX (6,7-dinitroquinoxaline-2,3-dione) and CNQX (6-nitro, 7-cyanoquinoxaline-2, 3-dione) attenuated the quisqualate-induced response. 6,7-Dinitroquinoxaline-2,3-dione also attenuated the d-serine-induced increases in levels of cGMP in a competitive manner. Intracerebellar injection of DNQX also antagonized the response to parenterally-administered harmaline. Similar results were also obtained with CNQX. These results indicate that these quinoxalinediones can attenuate the responses, mediated through the NMDA-associated glycine recognition sites, as well as the NMDA receptor complex. However, the glycine antagonist HA-966 (3-amino-1-hydroxypyrrolidone-2), at doses which completely reversed the increases induced by d-serine, failed to alter the response to quisqualate, indicating a lack of effect of glycine antagonists on quisqualate-mediated synaptic events. These results further support the interaction of the quinoxalinediones, DNQX and CNQX, with the NMDA receptor complex as established in receptor binding and electrophysiological studies.

Original languageEnglish (US)
Pages (from-to)1031-1035
Number of pages5
JournalNeuropharmacology
Volume29
Issue number11
DOIs
StatePublished - Nov 1990
Externally publishedYes

Keywords

  • CNQX
  • DNQX
  • NMDA-associated glycine receptor

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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