Protective effect of KBT-3022, a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia.
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.
Yamamoto
N
N
New Drug Research Laboratories, Kanebo, Ltd, Osaka, Japan.
Yokota
K
K
Yoshidomi
M
M
Yamashita
A
A
Oda
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011758:Pyrroles; D013844:Thiazoles; C064847:KB 3022; D000255:Adenosine Triphosphate