Protective Effect of KBT-3022, a New Cyclooxygenase Inhibitor, in Cerebral Hypoxia and Ischemia

The Japanese Journal of Pharmacology

Koichi Yokota²  Akira Yamashita²  Minoru Oda¹  Noriko Yamamoto²  Mikio Yoshidomi² 

[1] Research Laboratories, Torii Pharmaceutical Co., Ltd.;New Drug Research Laboratories, Kanebo, Ltd.

关键词: Cyclooxygenase inhibitor;    KBT-3022;    Hypoxia;    Ischemia;    Cerebrovascular disorder;   

DOI  :  10.1254/jjp.69.421

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(47)Cited-By(6)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 CAI 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.

【 授权许可】

Unknown