PT  - JOURNAL ARTICLE
AU  - Masayasu Takahashi
AU  - Jian Wei Ni
AU  - Sachiko Kawasaki-Yatsugi
AU  - Takashi Toya
AU  - Sin-Ichi Yatsugi
AU  - Masao Shimizu-Sasamata
AU  - Kazuo Koshiya
AU  - Jun-Ichi Shishikura
AU  - Shuichi Sakamoto
AU  - Tokio Yamaguchi
TI  - YM872, a Novel Selective α-Amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Receptor Antagonist, Reduces Brain Damage after Permanent Focal Cerebral Ischemia in Cats
DP  - 1998 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 467--473
VI  - 284
IP  - 2
4099  - http://jpet.aspetjournals.org/content/284/2/467.short
4100  - http://jpet.aspetjournals.org/content/284/2/467.full
SO  - J Pharmacol Exp Ther1998 Feb 01; 284
AB  - YM872 {[2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate}, a selective, potent and highly water-soluble competitive α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, was investigated for its neuroprotective effect against focal cerebral ischemia in halothane-anesthetized cats. Cats were subjected to permanent occlusion of the left middle cerebral artery for 6 h, then sacrificed and examined histologically. The electroencephalogram and cerebral blood flow were monitored. Intravenous infusion of YM872 starting 10 min after the onset of ischemia at a rate of 2 mg/kg/h for 6 h markedly reduced the volume of ischemic damage by 61% (from 2604 ± 202 mm3 of the cerebral hemisphere in saline-treated cats to 1025 ± 277 mm3 in YM872-treated cats; P < .01), as assessed in 12 stereotaxically determined coronal sections. No significant differences were observed between YM872- and saline-treated cats concerning physiological variables including brain temperature. No precipitation of YM872 in the kidney was seen in any YM872-treated animal. The present data further support the notion that the AMPA receptor plays an important role in the progression of focal ischemic damage in a gyrencephalic model. This evidence for the neuroprotective efficacy of YM872 suggests its therapeutic potential in the treatment of acute stroke in humans. The American Society for Pharmacology and Experimental Therapeutics