Clobazam (CLB, 1,5-benzodiazepine, 1,5-BZP) has been reported to show unique antiepileptic
action profile distinguishing from standard 1,4-BZPs. To further elucidate the action
profile of CLB, its effects on the abnormal circling fits (ACFs) and generalized tonic-clonic
convulsions (GTCs) in Ihara epileptic rats (IERs), a genetically epileptic mutant,
were examined in comparison with conventional antiepileptic drugs (AEDs), a 1,4-BZP,
clonazepam (CZP) and a non-BZP, zonisamide (ZNS).
The incidence of ACFs or GTCs in IERs was recorded automatically by the computer-assisted
behavior monitoring system (COBAS N-IV) before, during and after the drug treatment
period for 5 days in each. The drugs were orally administered twice daily. The daily
and total incidences of ACFs or GTCs were calculated every each period in each dose
group. The incidences of various behaviors such as feeding, gnawing and scratching
recorded simultaneously were used for evaluating the behavioral activity (BA).
CLB (30 and 60 mg/kg) prevented the appearance of ACFs and GTCs without affecting
BAs. CZP (1 and 3 mg/kg) suppressed the occurrence of ACFs but induced no effect on
the incidence of GTCs. Furthermore, it inhibited BAs at the same doses. ZNS (15 mg/kg)
suppressed GTCs but little ACFs without affecting BA.
CLB exhibited a different action profile from CZP and ZNS in a novel epileptic mutant,
IERs, and was expected to be a useful AED superior to 1,4-BZPs in clinical practice.