Novel NMDA/glycine site antagonists attenuate cocaine-induced behavioral toxicity

European Journal of Pharmacology
R R MatsumotoA G Kanthasamy

Abstract

N-Methyl-D-aspartate (NMDA)/glycine site antagonists were tested for their ability to prevent cocaine-induced convulsions and lethality in Swiss Webster mice. Pre-treatment of mice with the novel NMDA/glycine site antagonists ACEA-1021 (5-nitro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione) or ACEA-1328 (5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione) attenuated cocaine-induced convulsions; these effects were pharmacologically antagonized with D-cycloserine. The structurally-related NMDA/glycine site antagonist DCQX (6,7-dichloroquinoxaline-2,3-dione) and the structurally-unrelated NMDA/glycine site partial agonist HA-966 (3-amino-1-hydroxy-2-pyrrolidinone) also attenuated cocaine-induced convulsions, with the R(+)-isomer of HA-966 being more effective than the S(-)-isomer. In contrast, the selective alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist, NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide) , failed to provide statistically significant protection although it shares the 2,3-quinoxalinedione structure of DCQX and the ACEA compounds. Pre-treatment with ACEA-1021, ACEA-1328, DCQX, or R(+)-HA-966 also attenuated cocaine-induced lethality in mice. Signific...Continue Reading

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Citations

Nov 13, 2003·European Journal of Pharmacology·Beatriz A Rocha
Dec 4, 2003·Pharmacology, Biochemistry, and Behavior·Eric D CollinsRichard W Foltin
May 20, 1999·European Journal of Pharmacology·K A McCrackenR R Matsumoto
Mar 10, 2000·European Journal of Pharmacology·A Y BespalovR L Balster
Nov 12, 2009·Pharmacological Reports : PR·Dorota NieoczymPiotr Wlaź
Nov 8, 2011·Epilepsy & Behavior : E&B·Mehdi Ghasemi, Steven C Schachter
May 22, 2001·Experimental Biology and Medicine·K K ParkK F Soliman
Mar 12, 2011·The American Journal of Forensic Medicine and Pathology·D Kimberley Molina, Veronica M Hargrove
Dec 14, 2004·CNS Drug Reviews·Margaret A PettyKenneth I Maynard

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