A novel glycine site-specific N-methyl-D-aspartate receptor antagonist prevents activation of the NMDA/NO/CGMP pathway by ammonia

Brain Research
W HilgierJan Albrecht

Abstract

Intrastriatal administration of ammonium ions ("ammonia") via a microdialysis probe overactivates N-methyl-D-aspartate (NMDA) receptors, which results in cGMP accumulation in the microdialysates. Co-administration of a potent glycine site-specific NMDA receptor antagonist CGP 78608 ([(1S)-1-[[(7-bromo-1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]amino]ethyl]phosphonate) significantly reduced (at 20 nM) or abolished (at 100 nM) ammonia-dependent cGMP synthesis. Since NMDA receptor activation is an important causative factor in ammonia neurotoxicity, the present results suggest the glycine site of the receptor to be a potential valuable target for protective intervention.

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Citations

Feb 3, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jan Albrecht
Jan 5, 2014·Metabolic Brain Disease·Magdalena ZielińskaJan Albrecht
Aug 18, 2009·Brain Research Bulletin·Birgit NimmervollHubert H Kerschbaum
May 12, 2009·Neurochemistry International·Regina RodrigoVicente Felipo
Dec 17, 2009·Journal of Neurochemistry·Nisrin ElMliliVicente Felipo
Mar 7, 2006·Neurochemistry International·Agnieszka KonopackaMagdalena Zielińska
Jul 27, 2010·Biochemical Pharmacology·Jan AlbrechtMichael D Norenberg
Jul 29, 2016·Neurochemical Research·Simo S OjaEsa R Korpi
Apr 28, 2009·European Journal of Pharmacology·Uta Muth-SelbachPeter Lipfert
Mar 3, 2010·Metabolic Brain Disease·Carmina MontoliuVicente Felipo
Dec 31, 2005·Metabolic Brain Disease·Jan Albrecht, Michał Wegrzynowicz

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