TY - JOUR T1 - Neuroprotective Efficacy of YM872, an α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid Receptor Antagonist, after Permanent Middle Cerebral Artery Occlusion in Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 559 LP - 566 VL - 287 IS - 2 AU - Masayasu Takahashi AU - Jian Wei Ni AU - Sachiko Kawasaki-Yatsugi AU - Takashi Toya AU - Chikako Ichiki AU - Shin-Ichi Yatsugi AU - Kazuo Koshiya AU - Masao Shimizu-Sasamata AU - Tokio Yamaguchi Y1 - 1998/11/01 UR - http://jpet.aspetjournals.org/content/287/2/559.abstract N2 - The neuroprotective efficacy of YM872, a novel, highly water-soluble α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, was investigated in rats subjected to permanent occlusion of the left middle cerebral artery. The rats were assessed either histologically or neurologically 24 hr or 1 wk after ischemia. YM872 was intravenously infused for either 4 or 24 hr at dose rates of 0 to 20 mg/kg/hr starting 5 min after ischemia to examine the effect of prolonged treatment. YM872 was then infused at 20 mg/kg/hr beginning 0 to 4 hr after ischemia to determine the efficacy time window. Additionally, a 20 mg/kg/hr dose rate of YM872 was infused for 4 hr in single day- or 5-day repetitive-administrations to evaluate long-term benefits of the drug. YM872 significantly reduced infarct volume in both 4- and 24-hr treatment groups measured 24 hr after ischemia. No difference was observed in the degree of protection between length of infusion. Significant neuroprotection was maintained even when drug administration was delayed up to 2 hr after ischemia. A single YM872-administration significantly improved neurological deficit and reduced infarct volume (30%, P < .01) measured 1 wk after ischemia. YM872 treatment did not induce such adverse effects as physiological changes, serious behavioral abnormalities or nephrotoxicity. These data suggest that the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor plays a crucial role in the progression of neuronal damage in the early phase of ischemia and that YM872 may be useful in treating acute ischemic stroke. The American Society for Pharmacology and Experimental Therapeutics ER -