Katsuta K, Nakanishi H, Shirakawa K, Yoshida K, Takagi K, Tamura A
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
J Cereb Blood Flow Metab. 1995 Mar;15(2):345-8. doi: 10.1038/jcbfm.1995.40.
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.
本研究旨在比较新型非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂FR115427与（+）MK-801对大鼠局灶性脑缺血的神经保护作用。通过永久性闭塞左侧大脑中动脉（MCA）制备局灶性脑缺血模型。缺血后立即腹腔注射给药，连续6天，每天1次。FR115427（10mg/kg，腹腔注射）在缺血后1天显著改善神经功能缺损，并在缺血后7天减少总梗死体积（54%）。尽管FR115427（10mg/kg，皮下注射）产生了与（+）MK-801类似的神经元空泡化，但与（+）MK-801不同，FR115427未产生体重减轻、死亡率和体温过低等不良反应。这些结果表明，FR115427可能对中风治疗有用。
