Actinomycin Dの高等動物中枢神経系に対する作用

1.Actinomycin Dをイヌの髄液内に投与すると,3～5日の長い潜時で動物は全身痙攣を起こした.この痙攣量は0.025mgであり,それによって42例中33例に痙攣が見られ,その平均潜時は89.5±10時間であった.痙攣型は定型的な全身痙攣であり,動物は激しく痙攣を繰返したのち全例死に至った.2.Actinomycinic acidを髄液内に投与しても痙攣は認められなかった.3.ネコの髄液内にactinomycin Dを投与して数日後に,動物は脳波上定型的なgeneralized seizure dischargeを反復して示した.この場合まず高振幅spikeの群発が起こり,これにspike and waveまたはpolyspike and wave complexがつづいた.やがてspike and wave complexの出現頻度がしだいに減少し,発作波が終了した.またactinomycin D投与により, hippocampusに顕著なspike dischargeが見られることがあった.また痙攣前駆期において,myoclonic jerkの発生と同時に,hippocampusを除く全誘導に8cpsの規則的な波が見られた.他方,actinomycinic acidの投与によっては,脳波上にも顕著な変化はあらわれなかった.4.Actinomycin Dと同時にDNAを髄液内に投与し,その拮抗作用の有無をしらべたが,このDNAの投与によっては, actinomycin D痙攣は防止できなかった.5. Actinomycin Dとmethionine sulfoximineとの干渉作用を検討し,痙攣閾量以下のmethionine sulfoximineはactinomycin Dの痙攣作用を妨げないが,逆に痙攣量の半量付近のactinomycin Dはmethionine sulfoximineの痙攣作用を抑制することを観察した.6. GABA,GABOB,S-GABAのactinomycin D痙攣に対する確実な抑制作用は,ほとんど認められなかった.

When a dose of actinomycin D was intrathecally injected into higher animals (dogs and cats), these animals experienced generalized seizures after a latent period of several days. The critical seizure producing quantity was 0.025mg on the dog. Actinomycin D combines with DNA in the nervous tissue of the brain, this may be the cause of the seizure effect. When the same dose (0.025mg) of actinomycinic acid, which has a chemical structure resembling that of actinomycin D, but does not combine with DNA in the tissue, was injected into the cerebro-spinal fluid of the dog, the animals did not show any behavioural change. Electroencephalographic studies of the actinomycin D seizure were carried out on the cat. Several days after the administration of actinomycin D, the animal showed the typical generalized seizure discharges. A generalized seizure discharge induced by actinomycin D began with the occurrence of frequent spikes in group in all of recording sites, then the repetition of a spike and wave complex or a polyspike and wave complex followed. The intervals of each spike and wave complex gradually grew longer, and the seizure discharge stopped. After the actinomycin D administration, the electroencephalogram sometimes showed remarkable spike discharges occurring in the hippocampal region. They occurred mostly in hippocampus, but to a lesser degree spike discharges occurred in the other regions. In the preconvulsive state after the actinomycin D administration, regular waves of 8 cps occasionally appeared simultaneously with the occurrence of myoclonic jerks. In the case of the injection of actinomycinic acid into the cat, no significant change occurred on the electroencephalogram. However, the injection of DNA into the cerebrospinal fluid, simultaneously performed, with the injection of actinomycin D, did not stop the seizure effect of the latter. Methionine sulfoximine, characterized by a seizure effect with a long latent period, was also injected into the cerebro-spinal fluid of the dog. The critical seizure producing quantity was 0.18mg. These two convulsants with long latent period, the actinomycin D and the methionine sulfoximine, did not produce seizure effects when combined in different proportions. Three butyric acid derivatives (GABA, GABOB and S-GABA) did not arrest the actinomycin D seizure effect.