A novel AMPA receptor antagonist, YM872, reduces infarct size after middle cerebral artery occlusion in rats

Brain Research
S Kawasaki-YatsugiK Minematsu

Abstract

The neuroprotective effect of YM872 ([2.3-dioxo-7-(1H-imidazol-1-yl) 6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate), a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist with improved water solubility, was examined in a rat focal cerebral ischemia model. Rats were subjected to permanent middle cerebral artery (MCA) occlusion using the intraluminal suture occlusion method for 24 h. YM872 was intravenously infused for 4 h (20 and 40 mg/kg/h) or 24 h (10 and 20 mg/kg/h), starting 5 min after the MCA occlusion, to investigate the effect of prolonged duration of the treatment on infarct volume. In the 4 h infusion study, YM872 reduced the cortical infarct volume by 48% at a dose of 40 mg/kg/h. YM872 did not significantly reduce the infarct at 20 mg/kg/h for 4 h. In the 24 h infusion study, however, YM872 markedly reduced the cortical infarct volume by 62%, even at 20 mg/kg/h. The present study indicates that the neuroprotective effect of YM872 is enhanced by extending the duration of treatment, and demonstrates the benefit of the prolonged treatment with AMPA antagonists following focal cerebral ischemia. YM872, a highly water soluble compound, is applicable to investigate the ...Continue Reading

Citations

Apr 30, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tsuyoshi MinematsuHidetaka Kamimura
Jul 9, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·T MinematsuH Kamimura
May 17, 2008·CNS Neuroscience & Therapeutics·Yoshinori KotaniHideaki Hara
Oct 25, 2014·Antioxidants & Redox Signaling·Savita KhannaCameron Rink
Oct 9, 2002·Current Medical Research and Opinion·Paul T Akins, Richard P Atkinson
Nov 2, 2004·Chemical & Pharmaceutical Bulletin·Kin-ya SohdaHidetaka Kamimura
Apr 2, 2008·Expert Opinion on Pharmacotherapy·K JeyaseelanA Armugam
May 9, 2002·Expert Opinion on Investigational Drugs·Jeffrey J LegosFrank C Barone
Jul 5, 2005·Expert Opinion on Therapeutic Targets·D L Small

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