Nizofenoneの脳保護作用に関する実験的検討

AN EXPERIMENTAL STUDY ON THE PROTECTIVE EFFECT OF NIZOFENONE IN CEREBRAL ISCHEMIA

　抄録　酸素需要，エネルギー消費の抑制作用のほか遊離基捕捉作用を有するとされるnizofenoneの虚血脳に対する脳保護作用を検討する目的で以下の実験を行った。実験モデルとしては脳血流量を灌流ポンプにより自在に調節できる"完全虚血脳灌流モデル犬"を用いて，薬剤の虚血前投与後，灌流血流量を正常時の1／10に低下させ，1時間持続した後，再び元の灌流量に戻し，その後の脳波の回復を観察することによって薬剤の効果を判定した。実験は無治療対照群5頭，nizofenone 1mg／kg投与群5頭，3mg／kg投与群5頭，10mg／kg投与群5頭の計4群に分けて行った。結果は，nizofenoneの投与量が多いほど，血流再開後の脳波の回復は良好であり，本剤の虚血脳保護効果は投与量依存性（dose dependent）であった。ただし本剤の大量投与時には一過性の血圧下降がみられ，この点が本剤を臨床応用する際の問題点になるかと思われた。

Using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the protective effects of nizofenone against cereb-ral ischemia was investigated.

After pre-treatment with nizofenone, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG activity were observed and the effect of nizofenone evaluated.

In the control group, no recovery of EEG was seen following recirculation, but in the group treated with nizofenone, gradual emergence of slow waves was observed. And the degree of re-covery of EEG was better in the group adminis-tered a large dosage than in those given a low dosage.

Our study suggested that within the dose ranges tested, nizofenone ameliorated ischemic brain da-mage in a dose dependent fashion. But the ap-plication of this experimental results to the human clinical situation requires that particular note should be paid to the dangers of transient fall of blood pressure at higher dosages.