Focal epilepsy modelに対するpenicillin Gの急性効果について

ACUTE EFFECT OF PENICILLING ON FELINE MODELS OF FOCAL EPILEPSY

　抄録　ペニシリン系抗生物質にけいれん誘発作用があることは良く知られている。今回，二つのfocalepilepsy model （amygdaloid kindling model, kainic acid-induced limbic seizure model）に対するpeni-cillin G （PC）の急性効果について検討した。control群では，PC （40〜60×10⁴unit／kg）腹腔内注入後，皮質にspike and wave dischargeが出現したが，臨床上では全身けいれんに進展することはなかった。amygdaloid kindling modelでは，PC （40〜60×10⁴unit／kg）腹腔内注入後1時間10分〜2時間30分で，33％の例に扁桃核発作から始まる二次性全般化けいれんが出現した。kainic acid-induced limblc seizuremodelでは，PC （15〜20×10⁴unit／kg）腹腔内注入後30〜50分で，全例に扁桃核発作から始まる二次性全般化けいれんが出現した。kindlingおよびKA microinjecitonによるepileptic focusではblood brainbarrierあるいはGABAergic neuronの障害が出現している可能性が示唆された。臨床上でも，focalepilepsyの症例にはPCの大量投与には慎重である必要があると考えられる。

Penicillin is well known as a potent convulsive agent. A cortical topical, intracerebral or systemic administration of penicillin produces abnormal and paroxysmal activity which may lead to seizure, and has been used in the investigation of the mecha-nisms of epilepsy. This is a report on the studies of an acute effect of potassium penicillin G on two models of experimental focal epilepsy : a) amy-gdaloid kindling model, and b) kainic acid-induced limbic seizure model.

Twelve adult cats for amygdaloid kindling model (kindling group), six for KA-induced limbic seizure model (KA group) and four for a control group were prepared for this study. In kindling group, after completion of kindling procedure, 40-60 × 10⁴ unit/kg of potassium penicillin G (PC), dissolved in sterilized normal saline, was injected intraperi-toneally during an interictal period. In KA group, 1 μg of KA was injected into the left amygdala. Limbic seizures occurred frequently during the ini-tial 5 hours but subsided completely within 3 days. After a latent period, spontaneous secondarily generalized convulsion occurred from 30 to 60 days after KA injection. The cats were completely normal in their behavior during the interictal period.

During the interictal stage after the first gene-ralized convulsion has been observed, 15-20 × 10⁴ unit/kg of PC was injected intraperitoneally. In the control group, 40-60 × 10⁴ unit/kg was injected intraperitoneally. Electroclinical observations were continued until 5 hours after PC injection in three groups. In the control group, no cats deve-loped generalized convulsion. In the kindling group, 4 of 12 cats developed focal amygdaloid seizures with secondary generalization by nearly the identical doses required in the control group. In the KA group, amygdaloid seizures occurred and resulted in secondary generalization in all the cats by a smaller amount of PC administration in comparison with the kindling group. The mean latency for seizure induction were about 110 min in the kindling group and 40 min in the KA group. In conclusion : 1) Intraperitoneal PC injection could produce secondarily generalized seizures in both experimental models of focal epilepsy ; amygdaloid kindling model and KA-induced limbic seizure model. 2) Epileptic focus induced by KA injection is more sensitive to PC than the focus induced by kindling.

These results indicate a possible risk of a large amount of PC administration to the patient with focal epilepsy.