title: The neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427 in focal cerebral ischemia in rats.
abstract: The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of(+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were administered intraperitoneally immediately after ischemia and once a day for 6 successive days. FR115427 (10 mg/kg, i.p.) significantly improved neurologic deficit at 1 day after ischemia and reduced total infarct volume (54%) at 7 days after ischemia. Although FR115427 (10 mg/kg, s.c.) produced neuronal vacuolization similar to (+)MK-801, FR115427 did not produce adverse effects such as a loss of body weight, mortality, and hypothermia, in contrast to (+)MK-801. These results suggest that FR115427 may be useful in the treatment of stroke.
authors.affiliation: New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Katsuta
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
authors.forename: K
authors.initials: K
authors.lastname: Shirakawa
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Takagi
authors.forename: A
authors.initials: A
authors.lastname: Tamura
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D044005:Tetrahydroisoquinolines
chemical_list: D007546:Isoquinolines; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D044005:Tetrahydroisoquinolines; C084456:1-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline; D016291:Dizocilpine Maleate