Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats.

Abstract

We studied the effect of a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2, 3(1H, 4H)-quinoxalinedione monohydrochloride], in a focal cerebral ischemia model using anesthetized cats. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. The amount of ischemic damage was assessed in 12 stereotaxic coronal sections. Treatment with YM90K (i.v. infusion of 0.5 mg/5 ml/kg/h) starting 10 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2823 +/- 164 mm3 of the cerebral hemisphere in saline-treated cats to 1737 +/- 305 mm3 in YM90K-treated cats). No essential differences were observed between YM90K-and saline-treated cats concerning physiological variables or brain temperature. These results further support the notion that the AMPA/kainate receptor plays an important role in the pathogenesis of focal cerebral ischemia. This evidence for the neuroprotective efficacy of YM90K in a gyrencephalic species suggests its therapeutic potential in the treatment of human stroke.

• Authors: S Yatsugi, M Takahashi, S Kawasaki-Yatsugi, K Koshiya, S Sakamoto, D Uematsu, M Shimizu-Sasamata
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 16 Issue 5 Pg. 959-66 (Sep 1996) ISSN: 0271-678X [Print] United States
• PMID: 8784240 (Publication Type: Journal Article)

Chemical References

• Quinoxalines
• Receptors, AMPA
• Receptors, Kainic Acid
• 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione

Topics

• Animals
• Blood Pressure
• Body Temperature
• Brain (physiopathology)
• Cats
• Electroencephalography
• Hydrogen-Ion Concentration
• Ischemic Attack, Transient (drug therapy, physiopathology)
• Male
• Neurons (physiology)
• Quinoxalines (blood, cerebrospinal fluid, therapeutic use)
• Receptors, AMPA (antagonists & inhibitors)
• Receptors, Kainic Acid (antagonists & inhibitors)