Sodium Di-N-propylacetate （DPA）のてんかん予防効果と抗けいれん効果について—Kindlingpreparationを用いた実験的研究

PROPHYLACTIC AND ANTICONVULSIVE EFFECTS OF DI-N-PROPYLACETATE EXAMINED IN KINDLING CAT PREPARATIONS

I．はじめに

　てんかんの治療はてんかん発作の抑制だけにとどまるものではない。非てんかん性の脳がしだいにてんかん原性を獲得していく過程や，難治性てんかんにみられる脳機能の慢性進行性の変化を阻止することが，てんかんのより木質的な治療であるといつても過言ではなかろう。ここ数年間，kindling preparationが有用なてんかんの実験モデルとして登場して以来，抗てんかん薬がもつ2つの異なる効果──抗けいれん効果および，進行性脳変化を阻止する予防効果──を明瞭に区別してとらえることが可能となつた^12,22,23）。さらに，これら2つの効果が必ずしも一致したものでないことも知られるようになつた。たとえば，carbamazepineやΔ⁹-tetrahydrocannabinolは発作の発展を強く阻止する効果（予防効果）をもつが，kindling effectとして形成された全身けいれん（kindledconvulsion）に対する抑制効果（抗けいれん効果）はそれほど著明ではない。また，kindled convulsionに軽い抑制効果をもつdiphenylhydantoinは，発作の発展には無効かむしろ促進的にはたらくと報告されている^17,23）。

　今回は，1963年Meunierら^5）によつて抗けいれん作用が発見されたSodium Di-N-propylacetate （DPA）について，その抗けいれん効果と予防効果を検討した。その結果，非中毒量のDPAが扁桃核発作の発展を阻止する予防効果をもち，皮質焦点発作と扁桃核発作のいずれに対しても同様の抗けいれん効果をもつことが示されたので報告する。

Prophylactic and anticonvulsive effects of sodium di-N-propylacetate (DPA) were examined in kind-ling cat preparations. DPA were administered intravenously at three minutes prior to daily electri-cal stimulations.

1) prophylactic effects ; All the DPA cats de-veloped to the generalized convulsive seizures after an average of 33.5 daily amygdaloid stimulations (25 during the drug session and 8.5 during therekindling session without drug), whereas the con-trol group developed to the generalized convulsions after an average of 17. 0 stimulations. 50 mg/kg of DPA also suppressed the prolongation of after-discharge (AD) duration and increase of AD ampli-tude during the kindling seizure development, but had no effect on the AD propagation from the stimulated site to secondary brain sites. A mean serum level at the stimulation was 206. 2 dug/ml and no toxic behavioral sign was observed. These finding showed potent prophylactic effects of DPA against the kindling amygdaloid seizure develop-ment.

2) anticonvulsive effects ; Three amygdaloid kindled cats and three temporal cortical kindled cats were used. 25, 50 and 100 mg/kg of DPA were injected intravenously at three minutes prior to the stimulation with final electroconvulsive threshold. 50 mg/kg of DPA suppressed both type of kindled generalized convulsions behaviorally and electrographycally, whereas 25 mg/kg of DPA sup-pressed the amygdaloid seizures slightly but did not suppress the temporal cortical seizures. Together with these findings, it was concluded that subtoxic dose of DPA has clear prophylactic effects to the amygdaloid seizure development and anticonvulsive effects to the amygdaloid and temporal cortical seizures.