髄腔内薬物投与法の研究—第1報：CDP-choline

STUDIES ON INTRATEIECAI, PHARMACOTHERAPY:CDP-CHOLINE

I．はじめに

　中枢神経系に対する薬物投与の経路としての髄腔内投与には全身的投与ではみられない特徴がある。脳には血液脳関門，髄液脳関門が存在すると考えられ，全身的投与では血液脳関門を通過しない薬物が多いので，髄腔内投与の方が中枢神経系に対してより強い薬理効果を現わす。しかし一方本法は副作用も著明であるため使用しうる薬物はかなり限定されている。われわれは種々の薬物の髄腔内投与法を検討しているが，なかでも脳賦活剤としてのCDP-cholineはアイソトープでラベルすると血管内投与では脳の放射活性はわずかであるのに，髄腔内投与では大母のアイソトープの脳内集積と，尿中排泄が緩慢であることが実験的に証明されており^6,14），臨床的に髄腔内投与の有用性を示唆している。

　一方，脳の病変に基づく意識障害の賦活には種々の薬剤が用いられているが，脳波を指標とした場合Hocka—day^5）の分類でGrade IV bないし，V a,bに対する賦活効果は未だ認められていない。

Seven cases showing disturbance of consciousnessdue to primary cerebral lesion were treated byintrathecal injection of CDP-choline. They included3 cases of severe head injury, 3 of ruptured intra-cranial aneurysm with vasospasm and one of sub-acute encephalitis. A dose of 125 or 250 mg ofCDP-choline was injected by lumbar puncture andthe EEG was recorded continuously.

The effect of intrathecal application of CDP-choline can be divided into two types, an immediateeffect appearing within two hours after injectionof CDP-choline, and a late effect which manifestsafter a day or more. Appearance of manifestations,such as yawning, opening the eyes and reactionto noxious stimuli, and improvement in EEG wereobserved as the immediate effect.

The late effect was composed of improvement ofneurological findings and the grade of EEG. Ina case with nearly flat EEG, appearence of theelectrical activity was denoted 2 days after theintrathecal injection of CDP-choline.

An experimental study using the technique ofwhole body autoradiography was carried out in therat. Absence of ¹⁴C-CDP-choline in the centralnervous system with intravenous application ofCDP-choline was found, and this fact indicates thatno CDP-choline was taken up by the central nerv-ous system via the blood-brain-barrier. On theother hand, a marked increase in radioactivity wasfound in the brain and the spinal cord one hourafter the intrathecal injection of ¹⁴C-CDP-choline.

In conclusion, it can be said that when CDP-choline is injected into the intrathecal space, it istaken up the brain tissue via the liquor-brain-barrierand produces a direct stimulating effect on thecentral nervous system.