Neuroprotective efficacy of YM872, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, after permanent middle cerebral artery occlusion in rats

The neuroprotective efficacy of YM872, a novel, highly water-soluble alpha-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 neurologica...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 1998-11, Vol.287 (2), p.559
Main Authors: Takahashi, M, Ni, J W, Kawasaki-Yatsugi, S, Toya, T, Ichiki, C, Yatsugi, S I, Koshiya, K, Shimizu-Sasamata, M, Yamaguchi, T
Format: Article
Language:English
Subjects:
Animals
Brain Ischemia - drug therapy
Brain Ischemia - pathology
Cerebral Arteries - pathology
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Amino Acid Antagonists - therapeutic use
Imidazoles - pharmacology
Imidazoles - therapeutic use
Male
Motor Activity - drug effects
Quinoxalines - pharmacology
Quinoxalines - therapeutic use
Rats
Rats, Inbred F344
Receptors, AMPA - antagonists & inhibitors
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Summary:The neuroprotective efficacy of YM872, a novel, highly water-soluble alpha-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
ISSN:0022-3565