YM90K, an AMPA Antagonist, Has No Neurotoxic Effects on Cerebrocortical Neurons in Rats

Izumisawa, Nobuyuki; Kawakami, Akio; Ohata, Takeji; Hanada, Takanori; Okeda, Riki

doi:10.1006/exnr.1995.1049

Cited by 11 publications

(2 citation statements)

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“…Ataxia was induced by NBQX in rats [15]. A potent AMPA receptor antagonist, YM 90K, has no psychotomimetic action and shows no histological changes in the rat brain [16]. However, the clinical application of AMPA receptor antagonists has been limited because of poor water solubility and nephrotoxicity caused by precipitation of the drug in the kidney [17].…”

Section: Discussionmentioning

confidence: 99%

Spinal neurotoxicity and tolerance after repeated intrathecal administration of YM 872, an AMPA receptor antagonist, in rats

Nishiyama

Kawasaki-Yatsugi²,

Yamaguchi³

et al. 2004

Journal of Anesthesia

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Section: Discussionmentioning

confidence: 99%

Spinal neurotoxicity and tolerance after repeated intrathecal administration of YM 872, an AMPA receptor antagonist, in rats

Nishiyama

Kawasaki-Yatsugi²,

Yamaguchi³

et al. 2004

Journal of Anesthesia

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“…A novel AMPA antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione], which has near-equal potency (K i =0.084 µM for [ 3 H]AMPA binding) to NBQX also showed neuroprotective effects in both global and focal cerebral ischemia models when administered during the post-ischemic period (ShimizuSasamata et al 1996;Yatsugi et al 1996;Kawasaki-Yatsugi et al 1997). AMPA antagonists also lack psychotomimetic actions and neurotoxicity (Izumisawa et al 1995) which some NMDA antagonists produce (Koek et al 1988;Olney et al 1991). These observations suggest that AMPA antagonists are good candidates as therapeutic agents to treat human stroke.…”

Section: Sachiko Kawasaki-yatsugi · Chikako Ichiki Shin-ichi Yatsugi mentioning

confidence: 99%

YM90K, an AMPA receptor antagonist, protects against ischemic damage caused by permanent and transient middle cerebral artery occlusion in rats

Kawasaki-Yatsugi¹,

Ichiki²,

Yatsugi³

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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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.

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The N -methyl- d -aspartate receptor channel blocker amantadine does not cause histopathological alterations in human brain tissue

Kornhuber¹,

Jellinger

Wiltfang³

et al. 1999

Acta Neuropathologica

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Low doses of N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonists induce morphological alterations in neurons of the cingulate gyrus and retrosplenial cortex of the rat. Neuronal cell death may result at higher doses. These effects are a major concern with regard to the introduction of new NMDA receptor antagonists into clinical trials. Amantadine is an uncompetitive NMDA receptor antagonist, which has been in clinical use for many years. In the present study we have looked for possible morphological alterations like necrosis in postmortem human brain tissue of patients previously treated with amantadine. Formalin-fixed tissue samples were taken from the hippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on previous amantadine medication and of 11 controls. Histopathological examination of sections was performed blind. All brains except one revealed either nonspecific age-related or cerebrovascular changes or other neurodegenerative disorders including Alzheimer's, Parkinson's or Lewy body disease. In conclusion, histopathological examination of the hippocampus, retrosplenial cortex, and cingulate gyrus of human brain did not reveal changes suggested to be specific for previous amantadine treatment.

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YM90K, an AMPA Antagonist, Has No Neurotoxic Effects on Cerebrocortical Neurons in Rats

Cited by 11 publications

References 0 publications

Spinal neurotoxicity and tolerance after repeated intrathecal administration of YM 872, an AMPA receptor antagonist, in rats

Spinal neurotoxicity and tolerance after repeated intrathecal administration of YM 872, an AMPA receptor antagonist, in rats

YM90K, an AMPA receptor antagonist, protects against ischemic damage caused by permanent and transient middle cerebral artery occlusion in rats

The N -methyl- d -aspartate receptor channel blocker amantadine does not cause histopathological alterations in human brain tissue

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