扁桃核キンドリングに及ぼす塩酸フルナリジンの急性効果について

ACUTE EFFECT OF FLUNARIZINE ON AMYGDALOID KINDLING IN CATS

　抄録　塩酸フルナリジン（Flu）の抗てんかん作用を猫の扁桃核キンドリング（AK）を用いて検討した。あわせてFluのバルプロ酸（VA）に対するadd-on効果についても検討した。23匹の猫を定位的，無菌的に手術をおこなった。扁桃核キンドリングのための刺激には，全経過を通してbiphasic square wave, pulse幅300μAの比較的強い刺激を用い，キンドリング完成後も確実に二次性全般化発作を誘発できるようにした。Flu単剤の場合は，30および50mg／kg,ip．の量では二次性全般化発作が抑制されたが，Fluの急性毒性のため3日以内に死亡した。しかし，安全域の3mg／kg,ip．以下の量では，抗てんかん作用はなかった。つぎに，FluのVAに対するadd-on効果について検討した。最も有効な組合せは，それぞれ単独では抑制効果がなかったFluの3mg／kg,ip．とVA100mg／kg,ip．で54.5％に二次性全般化発作の抑制が認められた。これらの結果は，Fluの抗てんかん薬としての作用を支持するものである。さらに，本研究で用いた"high intensity"kindlingは抗てんかん薬の効果を判定するのに有用であることを強調した。

Flunarizine (Flu), a difluoroderivative of cin-narizine, is well known as a calcium channel blocker. Recently, many authors have reported an antiepileptic effect of this drug in experimental models of epilepsy and in the clinical use. In the present study, acute effect of Flu was examined in the amygdaloid kindled cats, and add-on effects of Flu with valproic acid (VA) was also studied.

Twenty three cats were used in this study. Amy-gdaloid kindling was established as previously reported. A strength of stimulations for kindling was at 300 μA. Same strength was used after completion of kindling. In this "high intensity" kindling, daily stimulation invariably induced intial amygdalo-hippocampal seizures followed by secondarily generalized seizures after compeletion of kindling. In addition, one amygdaloid stimula-tion was given daily for 5 days after completion of kindling in order to make it certain to induce secondalily generalized seizures.

Drugs were injected on the 6th day intraperi-toneally one or two hours before the stimulation daily given for 5 days after completion of kind-ling (GS 6) or after 4 days clearance period of previous administration of the drug. Pretreatment with Flu (high doses : 30 or 50 mg/kg, i. p.) abo-lished the secondary generalization after the GS 6. With this high doses of Flu animals died of side effect within 3 days after intraperitoneal admi-nistration. With lower doses of Flu less than 3 mg/kg, i. p. of Flu no side effect was encountered but antiepileptic effect was not obtained as well.

Then add-on trials of Flu were performed with valproic acid (VA). The most effective combina-tion was 100 mg/kg, i. p. of VA with 3 mg/kg, i. p. of Flu. With this combination, secondary gene-ralization was suppressed at a ratio of 54. 5% The results confirmed antiepileptic effect of Flu and add-on effect of Flu to VA. Authors advocate that kindling with "high intensity" stimulation present-ed in this study is more precise and useful than ordinary kindling with stimulations of genera-lized seizure threshold in the study of the effect of anti-epileptic drugs.