新誘導体Ethoxycarbodiphenylhydantoinの抗てんかん作用

ON THE ANTIEPILEPTIC ACTIVITIES OF A NEW COMPOUND ETHOXYCARBODIPHENYLHYDANTOIN

I．まえがき

　現在使用されている抗てんかん剤の数は多いが，そのなかでもつとも広く用いられているものは，バービチュレイトとヒダントイン誘導体である。後者のうちからはアレビアチン（5,5—Diphenylhydantoin）やメサントイン（3—Methyl−5,5—phenylethylhydantoin）などのすぐれた抗てんかん剤がみいだされているが，これらには薬用量においても種々な副作用が認められており，その改善が強く望まれている。

　われわれ^1）はさきに，直鎖系誘導体の作用改善を企て，フェネトゥライドのN位置のアセチル化によつて得られるクランポールが，抗てんかん作用が強力で副作用の少ないことを知り，さらに同じ位置をethoxycarbo基で置換した新誘導体Ethyl　α—phenylbutyroyl allophanateが，強力な抗精神運動発作作用を示すことを報告した^2）。

We have previously reported that the introduction of ethoxycarboradical into the chemical structure of straight-chain compounds may improve their a nti-epileptic activities.

As the next step, we have tried to scrutinize the antiepileptic activities of a new compound Ethoxy-carbosubstituted derivative on 3-N position of 5,5- diphenylhydantoin which to date is accepted as one of the most potent anticonvulsants among hydantoins.

After confirming the lower toxicity and higher potencies in preventing electro- and metrazol-con-vulsions in comparison with 5,5-diphenylhydantoin on animals, we have administered this new com-pound upon 42 epileptics consisting mainly of chronic refractory cases with various seizure types.

Ethoxycarbodiphenylhydantoin has proved the most effective in grand mal type of seizures and controlled the seizures in 46,9% completely. It was also effec-tive in myoclonic and psychomotor seizures. As a whole its spectrum as an antiepileptic seemed rather similar to that of 5,5-diphenylhydantoin. Side-effects were also similar to those of 5,5-diphenylhydantoin, ataxia being the most frequent. Gum-hypertrophy has not been noticed so far. There have been often observed individual differences among the patients to these two drugs both in effects and side-effects and the determination of relative merits requires further studies.

However, the data compiled seems to show that this new compound is an effective anticonvulsant and to warrant clinical application.