The neuroprotective activity of the glycine receptor antagonist GV150526: an in vivo study by magnetic resonance imaging.
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.
Reggiani
A
A
Glaxo-Wellcome S.p.A., Research Laboratories, Verona, Italy.
Pietra
C
C
Arban
R
R
Marzola
P
P
Guerrini
U
U
Ziviani
L
L
Boicelli
A
A
Sbarbati
A
A
Osculati
F
F
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*
C105319:3-(2-((phenylamino)carbonyl)ethenyl)-4,6-dichloroindole-2-carboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D018696:Neuroprotective Agents; D018009:Receptors, Glycine