新誘導体Ethyl α—phenyl butyroyl allophanateの抗てんかん作用について

ON THE ANTIEPILEPTIC ACTIVITIES OF A NEW COMPOUND ETHYL α-PHENYL BUTYROYL ALLOPHANATE

I．まえがき

　てんかんは慢性難治の疾患であり，その治療には長期にわたる抗てんかん剤の服用が不可欠である。したがつて，バルビトウール酸誘導体の合成以来，ルミナールその他のすぐれた抗痙攣剤がみいだされ，さらにそれを端緒として多くの抗てんかん剤が発見されたにもかかわらず，現在もなお，より効果の高く，副作用の少ない新しい抗てんかん剤の探索が続けられているのは当然のことである。

　現在抗てんかん剤として用いられている薬剤は，その化学構造からみると種々なものがあるが，大部分はバルビトウール酸，ヒダントイン，オキサゾリジンなどの環状構造物の誘導体である。

In a series of research in seeking a safer and stronger substance in the straight-chain compounds which are probably effective for psychomotor epilepsy, we have known that Ethyl α-phenyl butyroyl allophanate has strong anticonvulsant properties in animal experiments.

The chemical structure of this compound is quite similar to that of Pheneturide, except that it has a ethoxy-carbo-radical on it's N-atom at the end opposite to phenyl-radical, and thus shows the structure of urethane at it's one end.

After confirming the low toxicity of the compound on animals, we have tried this new drug on 25 chronic epileptics with various seizure types, mainly psychomotor type, who have been refractory to all conventional an-tiepileptics hitherto administered.

From our clinical experiences we have known that this compound has a remarkable effec-tiveness for psychomotor seizures (effective in 60 %), whereas it's anticonvulsant activity against grand mal epilepsies was not so suf-ficient.

Side-effects such as gastrointestinal distur-bances or restlessness were observed, but they were slighter than those of Phenurone in comparison and disappeared soon after withdrawal: on the other hand, the incidence of neurotoxic symptoms such as ataxia see-med frequent.

We surmise, that characteristics of this new compound both in effectiveness and side-effects are closely related to it's chemical structure; i. e. the introduction of a ethoxy-carbo-radical on it's N-moiety seems to have strengthened the original action of a compound of this series.

We believe, therefore, that the introduction of a ethoxycarbo-radical into the antiepileptic substances is a prospective means of improv-ing their activities.