Clobazam shows a different antiepileptic action profile from clonazepam and zonisamide in Ihara epileptic rats.
OBJECTIVE
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).


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Miura
Yoshiki
Y
Safety Research Laboratories, Department of Safety Pharmacology, Dainippon Pharmaceutical Co., Ltd., 33-94 Enoki-cho, Suita, Osaka, Japan. yoshiki-miura@dainippon-pharm.co.jp
Amano
Shigeru
S
Torii
Ryuzo
R
Ihara
Nobuo
N
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D000078306:Clobazam; D002998:Clonazepam / Q000494:pharmacology / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D000078305:Zonisamide
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D007555:Isoxazoles; D001569:Benzodiazepines; D000078306:Clobazam; D000078305:Zonisamide; D002998:Clonazepam