Neuroprotective effects of a novel AMPA receptor antagonist, YM872.
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.
Small
D L
DL
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
Murray
C L
CL
Monette
R
R
Kawasaki-Yatsugi
S
S
Morley
P
P
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
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