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Protective Effect of KBT-3022, a New Cyclooxygenase Inhibitor, in Cerebral Hypoxia and Ischemia
- Source :
- Japanese Journal of Pharmacology. 69:421-428
- Publication Year :
- 1995
- Publisher :
- Elsevier BV, 1995.
-
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 (100mg/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.
- Subjects :
- Male
Cell Survival
Ischemia
Pharmacology
Hippocampal formation
Gerbil
Hippocampus
Brain Ischemia
Mice
Adenosine Triphosphate
Oral administration
medicine
Animals
Pyrroles
Enzyme Inhibitors
Hypoxia
Dose-Response Relationship, Drug
biology
business.industry
Cerebrovascular disorder
Cerebral hypoxia
Hypoxia (medical)
medicine.disease
Thiazoles
Anesthesia
biology.protein
Cyclooxygenase
medicine.symptom
business
Subjects
Details
- ISSN :
- 00215198
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Japanese Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....8cc63c5ae18f2a80e3b5447f804fc9db