てんかん動物(SERとNER)を用いた抗てんかん薬の評価

Abstract

Epileptic model animals, Spontaneously epileptic rat (SER) and Noda epileptic rats (NER), were examined to determine if they were useful for the evaluation of acute and chronic antiepileptic drugs. SER is a double mutant (zi/zi, tm/tm) exhibits tonic convulsion and absence-like seizures. The antiepileptic profile of a single application of conventional drugs in SER was similar to those found in human epilepsy. Novel antiepileptics such as topiramate, clobazam, and piracetam were successfully evaluated with SER for their anticonvulsant effects. The antiepileptic effects of repeated administrations of novel drugs could also be evaluated with this animal. The long-lasting effects of the antiepileptics were similar to those in human epilepsy. In SER hippocampal slices, long-lasting depolarization shift accompanying repetitive firing obtained in CA3 pyramidal cells with a single stimulation of the mossy fibers was inhibited by topiramate, but the firing induced by applying a depolarizing pulse in the cell was not affected, suggesting that the drug interferred with synaptic transmission in the mossy fiber-CA3 system of SER. Thus SER can also be empolyed for elucidating the mechanisms underlying the antiepileptic effects of the drug in question. Recently, a novel epileptic model animal NER, was developed. The clinical features resemble the tonicclonic seizures in human epilepsy. Multiple high voltage spikes appear in cotical EEG during seizures. The audiogenic seizures were induced by acoustic priming of a bell sound which had been given weekly to the NER since 3 weeks of age. This audiogenic seizure was inhibited by the conventional antiepileptics. Thus, both SER and NER are useful models for evaluating the acute and chronic antiepileptic effects of novel drugs.