Diphenylhydantoinによる小脳の電気生理学的反応

ELECTROPHYSIOLOGICAL RESPONSES OF CEREBELLUM AFTER THE ADMINISTRATION OF DIPHENYLHYDANTOIN

Ⅰ．はじめに

　Diphenylhydantoin （以下DPH）は，1908年Bilzによつて合成され，1938年にMeritとPatnumにより，抗てんかん作用のあることが発見された（Eadie^9）による）。それ以来，最も有効な抗てんかん薬のひとつとして，今日まで広く用いられてきた。DPHの電気生理学的な面における作用機序は，これまでいくつかの研究が報告されてきたが^{3,17,21,23〜25）}，まだ十分に解明されたとは言いがたい。

　DPHは大量投与により小脳失調をきたすこと，また長期間DPHを服用したてんかん患者の剖検例で，小脳萎縮を認める例があることなどから^2,6,13,15），これまで小脳との親和性が注目されてきた。

Experiments were performed to see the mecha-nism of anticonvulsive action of Diphenylhydantoin (DPH) especially in relation to the cerebellum.

15 normal adult cats were devided into three groups. After the intravenous administration of 10 mg, 20 mg and 30 mg/kg of DPH in each group, electrophysiological responses of the cerebellum with regard to Purkinje cell action potentials and the cerebellar electrocorticogram were observed for two hours. Purkinje cell action potentials were evaluated in its discharge rates, which were calcu-lated with medical computer. The cerebellar electrocorticogram were analyzed with Fast Fourier Transform method especially in its Adrian rhythm (150-250).

It has been demonstrated that Purkinje cell dis-charge rates increased extremely after a transient suppressed phase, but fast waves of the cerebellar electrocorticogram showed no remarkable changes following the administration of DPH. Plasma DPH concentration went up to a toxic level immediately after DPH injection, but returned to the plateau level after ten to thirty minutes which gradually decreased for two hours. Distribution of DPH was always higher in the cerebellum than in the cerebrum.

Recent experimental and clinical studies are suggesting that the cerebellum acts as one of the important intrinsic inhibitory systems against epilepsy.

Our results seem to imply that DPH exerts its anticonvulsive effect by potentiating inhibitory mechanism of Purkinje cells over the cerebral cortex.

The cerebellar electrocorticogram and the Purkinje cell unit activities showed no definite correlative responses to DPH administration. This will suggest that cerebellar electrocorticogram is not the only reflection of the Purkinje cell activity but the total electrophysiological phenomena of the cere-bellar cortex.