The neuroprotective activity of
GV150526 (3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-
carboxylic acid sodium salt), a selective
glycine receptor antagonist of the
NMDA receptor, has been evaluated by magnetic resonance imaging (MRI) in a rat model of
middle cerebral artery occlusion. The aim of the work was to evaluate, using an in vivo method, whether
GV150526 was able to reduce the extent of ischemic brain damage when administered both before and after (6 h)
middle cerebral artery occlusion.
GV150526 was administered at a dose of 3 mg/kg i.v. T2-weighted (T2W) and diffusion weighted (DW) images were acquired at 6, 24 and 144 h after the establishment of the
cerebral ischemia. Substantial neuroprotection was demonstrated at all investigated time points when
GV150526 was administered before the ischemic insult. The ischemic volume was reduced by 84% and 72%, compared to control values, when measured from T2W and DW images, acquired 24 h after
middle cerebral artery occlusion. Administration of the same dose of
GV150526, 6 h post-
ischemia, also resulted in a significant (p < 0.05) neuroprotection. The ischemic volume was reduced by 48% from control values when measured from T2W images and by 45% when measured from DW images. No significant difference was found between volumes of
brain ischemia obtained by either MRI or
triphenyltetrazolium chloride staining. These data confirm the potential neuroprotective activity of the
glycine receptor antagonist
GV150526 when administered either before or up to 6 h after
ischemia.