YM90K, an AMPA receptor antagonist, protects against ischemic damage caused by permanent and transient middle cerebral artery occlusion in rats.
The neuroprotective effect of YM90K, a potent AMPA receptor antagonist, was examined in rats with permanent and transient occlusion of middle cerebral artery (MCA) using intraluminal suture occlusion method. In rats with permanent MCA occlusions, two types of occluders were used to compare the efficacy of YM90K. When a 4-0 (diameter: 0.19 mm) suture was used, YM90K (20 mg kg(-1) h(-1) i.v. infusion for 4 h) significantly reduced infarct volume (P<0.05) and neurologic deficits (P<0.05) 24 h after MCA occlusion. Infarct volume was also reduced by YM90K at the same dose (P<0.01) when severe ischemia was induced by a 3-0 (diameter: 0.23 mm) suture. In rats with transient (3 h) MCA occlusions, a 10-mg kg(-1) h(-1) dose of YM90K that did not show significant protection in rats with permanent MCA occlusion offered neuroprotective effects. These data demonstrate that YM90K provides cerebral neuroprotection against a wide range of ischemic insults.
Kawasaki-Yatsugi
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S
Neuroscience Research, Pharmacological Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. yatsugis@yamanouchi.co.jp
Ichiki
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C
Yatsugi
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S
Shimizu-Sasamata
M
M
Yamaguchi
T
T
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011810:Quinoxalines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione