新しい抗てんかん剤3—Ethoxycarbo−5,5—diphenylhydantoin （P−6127）の使用経験

TREATMENT OF EPILEPSY WITH 3-ETHOXYCARB0-5,5-DIPHENYL-HYDANTOIN (P-6127), A NEW ANTICONVULSIVE AGENT

I．まえがき

　1938年MerrittとPutnam^3）によつててんかんの治療に導入されたdiphenylhydantoin （Aleviatin）はphe—nobarbital （Luminal）とともに，今日なお抗てんかん剤の主座を占めている。当初用いられたnatrium塩は胃腸障害がいちじるしかつたが非natrium塩にかえることによつてこの副作用が除かれた。しかしなお発熱，発疹，頭重，めまい，複視，歩行失調，眼振のほか，長期連用にさいして歯肉増殖や体毛増生などの副作用があつて，治療のさまたげとなつている。

　このため，より有効な，そしてより副作用の少ない抗てんかん剤開発の一環として，多数のhydantoin誘導体が実験的臨床的screeningにかけられ，Mesantoin，Ethotoin,N3（1—methyl−5,5—phenyl-ethyl-hydantoin）などが臨床的に使用されたが，あるものは副作用が強いため放棄され，あるものは効果が弱い欠点があつたりして，diphenylhydalltoinにまさるものはまだ出現していない現状である。

3-Ethoxycarbo-5,5-diphenylhydantoin (P-6127), a new anticonvulsant obtained by attaching an ethoxy-carbo radical to the N atom at position of 5,5- diphenylhydantoin (Aleviatin), has been tried on 25 epileptic patients with various seizure types, mainly grand mal type.

The results obtained were as follows:

1) P-6127 was effective on grand mal in appro-ximately 85%, complete control being effected in 6 cases. On focal seizures (including Jacksonian sei-zures) it was effective in all the four patients, 2 cases being completely controlled and the seizure reduced to less than a half in two cases. It proved effective either moderately or slightly in all the three cases of psychomotor seizure, though not completely in any. It was ineffective on such seizure types as petit mal, tonic convulsion and myoclonus epilepsy, but controlled one case of autonomic seizure com-pletely.

2) It gave slight improvement to the epileptic psychical disturbances and the electroencephalographi-cal abnormalities.

3) In 8 out of the 25 cases there were observed such side effects as ataxia, disturbance of speech, drowsiness, inactivity, loss of appetite, general mala-isia and nystagmus, but most of them were found to he transient and didn't necessitate discontinuation of the treatment. No instance of hyperplasia of the gum or increase of the body hair was met with during the administration period of ten months and a half.

The laboratory tests revealed in some cases increa-se of the TTT-and ZTT-value, transient reduction of the white blood cell count and increase of serum Na and decrease of serum K, without showing any abnormal values of pathological significance.

4) Comparison of their therapeutic efficacy has shown P-6127 and Aleviatin to be almost equally powerful on epileptic seizures and have the same action spectrum, but the former to have somewhat weaker side effects.