title: Neuroprotective effects of a novel AMPA receptor antagonist, YM872.
abstract: Quinoxalinediones such as NBQX are neuroprotective in most models of cerebral ischemia but their poor solubility results in nephrotoxicity limiting their clinical utility. We have investigated the neuroprotective effects of a water soluble AMPA receptor antagonist, YM872, using two in vitro models. The viability of cortical cultures exposed to 400 microM AMPA for 15 min (16.4 +/- 2.6%; n = 10) was significantly (p < 0.05) increased (84.7 +/- 4.6%; n = 6) with YM872 (10 microM) in a concentration-dependent manner. Evoked post-synaptic response amplitudes in oxygen-glucose deprived hippocampal slices treated with 10 microM YM872 (3.5 +/- 0.3 mV; n = 27) were significantly different from untreated deprived slices (0.3 +/- 0.1 mV; n = 31, p < 0.05) and the CA1 neurons appeared viable using a confocal live/dead fluorescence assay with confocal microscopy. The neuroprotection seen with YM872 in vitro warrants further investigation in vivo.
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: D L
authors.initials: DL
authors.lastname: Small
authors.forename: C L
authors.initials: CL
authors.lastname: Murray
authors.forename: R
authors.initials: R
authors.lastname: Monette
authors.forename: S
authors.initials: S
authors.lastname: Kawasaki-Yatsugi
authors.forename: P
authors.initials: P
authors.lastname: Morley
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005333:Fetus; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005947:Glucose