Yamamoto N, Yokota K, Yoshidomi M, Yamashita A, Oda M
New Drug Research Laboratories, Kanebo, Ltd, Osaka, Japan.
Jpn J Pharmacol. 1995 Dec;69(4):421-8. doi: 10.1254/jjp.69.421.
The protective effect of KBT-3022 (ethyl 2-[4,5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) , a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia was studied and compared with those of indomethacin and acetylsalicylic acid (ASA). Oral administration of KBT-3022 (3-100 mg/kg) and indomethacin (3 and 10 mg/kg) significantly prevented KCN-induced death in mice, while ASA (100 mg/kg) had no effect. KBT-3022 (3 and 10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) significantly prolonged the survival time of mice subjected to normobaric hypoxia, while ASA (100 mg/kg, p.o.) had no effect. KBT-3022 (3-30 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly ameliorated delayed neuronal death in the gerbil hippocampal CA1 sector after occlusion of bilateral carotid arteries for 5 min, while ASA (300 mg/kg, p.o.) had no effect. KBT-3022 (10 mg/kg, p.o.) significantly inhibited ATP depletion in the gerbil hippocampus after a 1-min occlusion of bilateral carotid arteries, but had no effect on ATP depletion after a 5-min occlusion and the recovery during recirculation. These results show that KBT-3022 exerts protective effects against cerebral anoxia and hypoxia and ameliorates delayed neuronal death in the hippocampus. KBT-3022 may therefore be useful for prophylaxis of ischemic cerebrovascular disorders.
研究了新型环氧化酶抑制剂KBT-3022（2-[4,5-双（4-甲氧基苯基）噻唑-2-基]吡咯-1-基乙酸乙酯）对脑缺氧和缺血的保护作用，并与吲哚美辛和乙酰水杨酸（ASA）进行了比较。口服KBT-3022（3-100mg/kg）和吲哚美辛（3和10mg/kg）可显著预防小鼠因氰化钾诱导的死亡，而ASA（100mg/kg）则无此作用。KBT-3022（3和10mg/kg，口服）和吲哚美辛（10mg/kg，口服）可显著延长常压缺氧小鼠的存活时间，而ASA（100mg/kg，口服）则无此作用。KBT-3022（3-30mg/kg，口服）和吲哚美辛（3mg/kg，腹腔注射）可显著改善沙土鼠双侧颈动脉闭塞5分钟后海马CA1区的迟发性神经元死亡，而ASA（300mg/kg，口服）则无此作用。双侧颈动脉闭塞1分钟后，KBT-3022（10mg/kg，口服）可显著抑制沙土鼠海马中的ATP消耗，但对闭塞5分钟后的ATP消耗及再灌注期间的恢复无影响。这些结果表明，KBT-3022对脑缺氧和缺血具有保护作用，并可改善海马中的迟发性神经元死亡。因此，KBT-3022可能对缺血性脑血管疾病的预防有用。
