Jpn. J. Pharmacol. 69, 421-428 (1995)

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

Noriko Yamamoto (1), Koichi Yakota (1), Mikio Yoshidomi (1), Akira Yamashita (1) and Minoru Oda (2)

(1) New Drug Research Laboratories, Kanebo, Ltd., 5-90, Tomobuchi-cho 1-chome, Miyakojima-ku, Osaka 534, Japan
(2) Research Laboratories, Torii Pharmaceutical Co., Ltd., 2-1, Ohnodai 1-chome, Midori-ku, Chiba 267, Japan

Abstract: 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.

Keywords: Cyclooxygenase inhibitor, KBT-3022, Hypoxia, Ischemia, Cerebrovascular disorder

Copyright© The Japanese Pharmacological Society 1995

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