言語障害に対するクロールジアゼボキサイドの効果に関する臨床的並びに実験的研究

　Ⅰ．緒言

　Chlordiazepoxide（CDP）は下記構造式に見るように，Phenothiazine誘導体，或いはReserpinなどの様な自律神経遮断剤，その他従来普及されているMeprobamateなどのTranquillizerなどとは全く構造を異にした精神安定剤である。従つて自律神経遮断剤の様な催眠作用や，錐体外路症状を起さないし，また精神の静穏作用が強く，その10mgrはMeprobamateの200乃至400mgrに相当する。而も副作用は殆んどない。またMeprobamate，Chlorpromazine，Phenobarbital等と同様，マウスに対して抗痙攣作用を示し，マウス，猫に対して筋弛緩作用を持つている。動物の食欲に対して独特な亢進作用を持つていることも，他の静穏剤には見られない点である。本剤は，不安焦燥を除き，緊張を和げると云う反面，同時に憂欝な非活動的な状態から，正常な日常活動へ患者を復帰させることが出来る。即ち社会的活動や発語に対する意欲を増進するなど，麻酔作用とは逆に寧ろ精神的には賦活する作用がある。言語機能を内的言語を形成する心理機能と，之を音声言語として表出する生理機能とに分けて考えると，この両機能は密接不可分の関係にあり，何れか一方の些細な不調は直ちに他に影響して円滑な言語活動は阻害されよう。この際の心理機能には，脳に於ける高次且つ広汎な諸中枢が関与して居り，その障害が鋭敏に言語に反映する所から，言語によつてのみ心理的障害が診断される場合が多い。CDPがこの両機能の何れに，どの程度に作用するかは興味ある問題であるが，我々は今回種々の言語障害に之を使用して，少くとも臨床的には認むべき効果を収め得たが，更に動物実験により，その作用機転を追究してみた。即ち猫の脳内に自製深部電極を刺入し，新皮質，視床下部，内側膝状体，中脳網様体，内包，尾状核，淡蒼球等について刺激し，実験を行い，脳波，筋電図，心電図等を記録しつつ，本剤注射前後に於ける変化を観察し，若干の知見を得たので，茲に報告する次第である。

　Thirty three patients (26 males and 7 females) ranging in age from 2.5 to 29 years were treated with chlordiazepoxide (CDAP) for speech disorder. This group consisted of 23 stutterers, 4 cerebral palsy, 4 feeble-mindedness, 1 poliomyelitis and 1 psychic deafness. Improvements in the affection were noted in 24 of the 33 patients, representing an overall effectiveness of 73 percent. As a whole, the response was shown markedly in 8 patients, moderate in 14, undecided in 6 and unchanged or worse in 3. In the treatment of 23 stutterers a marked response was shown in 5 patients, moderate in 10, either unchanged or even worse in 2 and the results were undecidable in 6. In 4 cases of cerebral palsy the response was remarkable 2 while the remaining 2 proved to be moderate in effect; in 4 cases of feeble mindedness the response was remarkable in 1, moderate in 2 and the condition remained unchanged in 1. In the respective cases of poliomyelitis and psychic deafness the agent proved to be moderately effective which was shown by the ease with which they made their speech delivery.

　Animal experimentations were made with electroencephalographic study to determine what points in the brain the agent CDAP may be effective. Following Jasper's atlas 4 or 5 electrodes were inserted in the exposed. cat's brain for stereotropic studies; following results were obtained.

　1 No change was noted when the electrode toucthed the cortical area but by touching subcortical areas such as basal ganglion, hypothalmus, nucleus ventralis, nucleus lateralis, nucleus rubrum, corpus geniculatum and reticular formation stereotropism was induced. These tests were performed without the aid of the drug.

　2 After administration of the agent cortex stimulation changed this area to mainifest a drowsy pattern with slow waves in it.

　3 Administration of CDAP raises the threshold of stimulus of ischiatic nerve to such an extent as to arouse the evoked potential in the reticular formation.

　4 The threshold of stimulus of the ischiatic nerve was remarkably raised which was enough to induce the arousal waves to be manifested when EEG of the cortex was performed.

　5 The electromyogram (EMG) of the brachial biceps was remarkably reduced after the use of the drug.