1—Acetyl−3—phenylethylacetylurea （Crampol）の抗てんかん作用について

ON THE ANTIEPILEPTIC ACTION OF A NEW STRAIGHT-CHAIN COMPOUND 1-ACETYL-3-PHENYLETHYLACETYLUREA (Crampol)

まえがき

　周知のように，てんかんの薬剤療法にはPhe—nobarbitalを発端としたBarbiturates,Hy—dantoin誘導体，Oxazolidine誘導体，Succin—imide誘導体，その他種々な薬剤が用いられているが，その中にあつてHydantoin核が開環したと考えられるPhenacetylurea （Phenurone）などのいわゆる直鎖系誘導体の存在も無視できない。すなわち1949年Gibbs, Everett　＆　Rich—ards^1）はPhenuroneが，それまで薬剤による発作の抑制が困難であると考えられていた精神運動発作に対して，他の薬剤にみられない強力で特異的な効果をあげたと発表して以来注目をあび，その後Carterら^2），Davidsonら^3），De Jong^4），Tylerら^5）などの追試を経て各種のてんかん発作なかんづく精神運動発作に対する効果が確認され，抗てんかん剤としての地位を保つてきた。しかし反面，Phenuroneには副作用が多く，胃腸障害・全身倦怠感・睡気・頭痛・発熱・発疹などのほか，不眠・興奮・錯乱・てんかん性性格変化の増悪などのような精神面の副作用もみられ，またときとして急性肝障害のため致死的な経過をとつた例も経験されていて，Dreyer^6）のように最近ではPhenuroneの臨床的価値について懐疑的な意見をもつものもある。

　そこで，Phenuroneのこれらの欠点を改善するために，各国で種々な類似の直鎖系誘導体が合成され試用されてきた。

We have used a new straight-chain compound 1-Acetyl-3-phenylethylacetylurea (Crampol) on 44 refractory epilepsies with excellent results. This drug was found out by screening from nearly 300 related synthesized new compounds. It has strong anti-convulsant activities against electroshock and metrazol convulsions and has weak toxicity on animals. Our material consisted of 44 epileptics includ-ing 58 seizure types in total who had been refractory to the conventional antiepileptic drugs. From clinical experiences we knew that this compound has a strong anticonvulsant action upon such convulsions as grand mals, focal and Jacksonian seizures, but it proved most effective on psychomotor epilepsies. Of 18 cases of psychomotor seizures, 5 (27.8%) were entirely seizure free upon this drug and in 5 cases the number of seizures decreased to less than one third, and in another 5 cases to less than a half.

This drug entirely controlled seizures in 13 (22.1%) and was markedly effective in 22 (37.9%) of all 58 kinds of various seizure types, thus showing its pretty wide spectrum as an antiepilepticum.

The optimum dosage is 600-1200mg a day.

The side-effects observed were sleepiness, headache, ataxia, restlessness and gastroin-testinal disturbances, etc., but they were not serious and disappeared soon after withdraw-al. In general we had the impression that those side effects were slight compared with those by Phenurone.

We believe that Crampol can be a strong armamentarium in the treatment of epilepsy.