抗てんかん剤としてのTegretolの特異性—臨床経験ならびに基礎的研究

PREFERENTIAL ACTION OF TEGRETOL (G-32883) TO LIMBIC SEIZURE:Clinical and Experimental Analyses

I．緒言

　1961年Geigy研究所のSchindlerら^21）によつて合成されたG32883，すなわちTegretolは翌年ミュンヘンで開かれた第3回胴際精神神経薬理学会でBonduelleら^1）により，その基礎実験および臨床成績が報告されて以来，新しい抗てんかん剤として賞用されはじめ，わが国でも1965年以後いくつかの報告がなされている^{4）6）11）〜13）17）19）20）22）25）26）}。本剤は従来の抗てんかん剤とはまつたく異なった構造式，すなわち抗うつ剤であるTofrani1，精神身体調整剤であるInsidon近縁の構造をもち，向精神作用のほかに抗痙攣作用として特に精神運動発作または側頭葉性てんかん，それに大発作にすぐれた効果を発揮するうえに，てんかん性格変調にも好影響をもたらすといわれている。

　臨床的に抗てんかん剤を使用するにあたつては，その薬剤がてんかんのどの型に選択的抑制効果を示すかということは重要な問題である。私どもは本剤の臨床使用経験を分析し，さらに動物実験によりその選択的発作抑制様式を追究した。

1. Clinical analysis: Fifteen epileptics were treat-ed by daily dosage of 200 to 1200 mg of Tegretol for 3 to 15 months of period: 6 psychomotor, 1 autonomic, 2 focal, 4 grand mal, 1 headache and 1 grand mal combined with psychomotor in seizure types. They were diagnosed in electroencephalogra-phic examination in addition to clinical anamnesis. Marked antiepileptic effect was obtained in all 6 psy-chomotor and also in autonomic seizures. In case of the combined type, psychomotor seizure was alle-viated leaving the grand mal seizure intact. No effect was found in the resting group of focal, grand mal and headache seizure. EEG improvement was found in case of seizure alleviation : disappearance of abnormal seizure discharge and increment of nor-mal background activity.

2. Experimental analysis: Acute experiment was performed in unanesthetized cats in order to make an analysis for preferential antiepileptic action of Te-gretol. Tegretol was intravenously given in the so-lution of propylen glycol. After-discharge threshold for electrical stimulation was measured for indication of antiepileptic effect at various cerebral structures such as motor cortex, ventrolateral nucleus of the thalamus, lenticular nucleus and limbic structures. The antiepileptic action seemed to remain for almost 60 minutes, and 90 to 120 minutes after the admini-stration of 5 and 10 mg/kg respectively. In any dosage of administration, marked evidences were the best increment of after-discharge threshold at limbic structures and no change at the lenticular after-dis-charge threshold. The cortico-thalamic system also reacted to Tegretol, but the threshold increment was not large enough to compare with the one of the limbic system.

3. Conclusion: It is, thus, concluded that Tegretol preferentially ally acts to limbic structures in the anti-epileptic point of view, comparing with the action to the cortico-thalamic and lenticular structures.