The non-NMDA antagonists, NBQX and GYKI 52466, protect against cortical and striatal cell loss following transient global ischaemia in the rat.
The cerebroprotective action of non-NMDA receptor blockade has been assessed in a model of transient global ischaemia using NBQX, 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, and GYKI 52466, 1-(amino-phenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine. HCl. In Wistar rats, prior cauterisation of the vertebral arteries was followed by occlusion of the common carotid arteries for 20 min, with a 7 day survival period before histological evaluation. NBQX, 40 mg/kg, or GYKI 52466, 40 mg/kg, was administered intravenously starting directly after the end of carotid occlusion and ending 3 h later. Both compounds produced significant protection against selective cell loss in the striatum and cortex. Less consistent changes were seen in the hippocampus; protection by NBQX was significant in CA3 but neither compound produced significant protection in CA1. This pattern of protection is interpreted in terms of a blockade of glutamate's action at non-NMDA receptors limited to the initial 3 h of reperfusion.
Institute of Psychiatry, London, U.K.
E
E
Le Peillet
B
B
Arvin
C
C
Moncada
B S
BS
Meldrum
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D018698:Glutamic Acid