Tegretolの抗てんかんならびに向精神作用についての臨床経験

CLINICAL EXPGRIENCES OF TEGRETOL IN PSYCHOTROPIC AND ANTI CONVULSIVE EFFECT

I．はじめに

　近年，抗てんかん剤の開発にはめざましいものがあるが，しかし，各種の発作型およびそれらの混合型，いわゆるcombined seizureの大部分に対し，奏効するようなbroad spectrumを有し，とくに難治例にも有効であり，しかも，副作用の少ないといつた薬物はいまだ数を多くみないといつてよい。さらに，従来の抗てんかん剤の中には発作抑制によつて，かえつて種々の精神症状を悪化させるものが知られており，抗てんかん作用とともに向精神作用をあわせ持つ，新抗てんかん剤の出現が待たれていた。

　1953年，DomenjozらはMorelの合成したN-car—bamyl-iminodibenzyl （G26301）にすぐれた抗痙攣作用のあることをみいだしたが，引き続きその誘導体の研究がGeigy研究所で行なわれ，1961年，Schindlerら^1）によりIminostilbeneの誘導体が研究され，その一つとしてTegretol （G 32883）が合成されるにいたつた。Tegretolは水に不溶であるが，propyleneglycolには溶解する白色結晶の粉末で，その化学構成造式は第1図のごとくである。

Tegretol (5-Carbamyl-5H-dibenzo (b. f) azepin) was given in twenty cases including tweleve cases of severely controlled epilepsy. This experiment has led to the conclusion that the effects have been produced in 70% of the cases including seven cases in which seizure has completely disappeared. In regard with type of seizure, it has ,een mcst effective on psyc-homotor epilepsy and the effects have been produced in 87.5%, including four cases of complete suppres-sion. In grand mal seizure the rate of effectiveness was 86% including two cases in which the seizure completely disappeared. It has been reported to be lesse effective on petit mal seizure but the marked eff-ects have been obtained in one case of tweleve cases of myoclonic seizure. Thus this drug has the most effective anticonvulsive action for psychomotor and grand mal seizure and also effective on combined seizure. In addition psychotropic effect of this drug has been confirmed on the basis of clinical results and analysis of photoanalogram, and mental improv-ement has been observed in 55% of the cases.

On routine EEG and frequency analysis of EEG done in tweleve cases suppresion of slow wave factor and stability of rhythm have been observed by the administeration of this drug. This improvement on EEG has been observed more frequently in such cases in which the effects of this drug has been highly produced on suppression of seizure. The analy-sis of photoanalogram has, however, suggested that excessive administration of this drug would result in the appearance of lowering of the psychic activity and slowness of behavior. The mean dosage in this experiment was 690 mg/day and side-effects would not occur if it is within normal dosage. In regard with side-effects found in this experiment slight drowsi-ness has been the most frequent one which has been found in 40% and eruption, redness of face, photo-phobia and the like have been noted in a few cases but they were all transitory. This drug can be used in such severe cases in which Hydantoin derivatives could not be given because of the side-effects. In thirteen cases in which the single administration of this drug was given the effects have been produced on suppression of seizure in ten cases in more than 50% of the effective rate. Therefore, the anticonvul-sive action of this drug seemed to be excellent even if it was given by single administration.