A dose-response study of neuroprotection using the AMPA antagonist NBQX in rat focal cerebral ischemia.
AMPA antagonists have been shown to be remarkably neuroprotective in models of global ischemia, but the data in focal ischemia remain controversial. We, therefore, studied the dose-response characteristics and the time window of efficacy of the AMPA antagonist NBQX in a rat model of permanent focal ischemia. NBQX 40, 60 or 100 mg/kg i.v., substantially reduced infarct size. Neuroprotection was maintained when the initiation of drug administration was withheld for 15, 45 or 90 min after permanent middle cerebral artery occlusion. Furthermore, NBQX did not induce heat shock protein in cingulate cortex, as do some N-methyl-D-aspartate antagonists. Thus, the compound is a potent neuroprotectant in focal ischemia and has an unusually long time window of effectiveness.
Graham
S H
SH
Department of Neurology, University of Pittsburgh, Pennsylvania, USA.
Chen
J
J
Lan
J Q
JQ
Simon
R P
RP
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use* / Q000633:toxicity; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D006360:Heat-Shock Proteins; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate