Indeloxazine hydrochlorideの虚血脳でのエネルギーおよび糖代謝に対する作用について

EFFECTS OF INDELOXAZINE HYDROCHLORIDE ON BRAIN ENERGY AND GLUCOSE METABOLISMS IN FOUR-VESSEL OCCLUSION RAT MODEL

　抄録　Indeloxazineは各種実験モデルで記憶，学習改善作用を有する。Pulsinelli-Brierleyの方法により脳虚血モデルを作製し，Indeloxazineの脳虚血に及ぼす影響をエネルギーおよび糖代謝の面から検討した。Indeloxazineは60分虚血後60分再開通の実験系においてATPおよび総アデニン，ヌクレオチド含量を軽度増加した。Indeloxazineは60分虚血後60分再開通の対照群に比べ軽度ながら14C−2-deoxyglucose代謝の改善作用を示した。特に海馬，皮質および視床等の一部で比較的高い14C−2-deoxyglucose代謝を示した。IndeloxaznieはPulsinelli-Brierleyの方法による脳虚血モデルにおいて脳保護的に作用していると考えられた。

Indeloxazine hydrochloride (Indeloxazine) has been known as a new type drug with enhancing effects on memory and learning processes in various experimental models. In the present studies, effects of Indeloxazine on brain energy and glucose metabolisms were determined in four-vessel occlusion rat model. Since a critical point of ischemic time for the recovery of brain energy levels existed between 30min and 60min in this model, effects of Indeloxazine were de-termined in the rat model of 60min recirculation following 60 min ischemia. One-week dosing of Indeloxazine at 2mg/kg showed slight increases in ATP and total adenine nucleotides levels. To elucidate the mechanism of improving action of Indeloxazine on brain energy levels, effects on glucose metabolism were determined. Non-treated group of 60min ischemia-60min recircula-tion showed severe reduction of ¹⁴C-2-deoxy-glucose metabolism in comparison to normal control group. Indeloxazine-treated group showed a slight improvement of ¹⁴C-2-deoxyglucose metabolism in comparison to non-treated group. Furthermore, high ¹⁴C-2-deoxyglucose metabo-lism was observed in parts of hippocampus, cortex and thalamus. From these results, it seems possible that Indeloxazine has some protective effects on brain damage in four-vessel occlusion rat model.