RRC ID 163
Author Ji-qun C, Ishihara K, Nagayama T, Serikawa T, Sasa M.
Title Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): differentiation of levetiracetam from conventional antiepileptic drugs.
Journal Epilepsia
Abstract PURPOSE:Some evidence suggests that levetiracetam (LEV) possesses antiepileptogenic characteristics. The purpose of this study was to investigate the time course of seizure protection by LEV compared with that of phenytoin (PHT), phenobarbital (PB), valproate (VPA), and carbamazepine (CBZ) in the spontaneously epileptic rat (SER). The SER is a double mutant (tm/tm, zi/zi) showing both tonic convulsions and absence-like seizures.
METHODS:The effect of single (40, 80, and 160 mg/kg, i.p.) and 5-day (80 mg/kg/day, i.p.) administration of LEV on tonic convulsions and absence-like seizures in SERs were studied. Tonic convulsions induced by blowing air onto the animal's head at 5-min intervals for 30 min and spontaneous absence-like seizures characterized by 5- to 7-Hz spike-wave-like complexes in the cortical and hippocampal EEG were recorded for 30 min. In the single-administration study, observations for seizure activity were performed once before and 3 times (45, 75, and 135 min) after drug administration. In the 5-day administration study, seizure observation was performed 4 times for 30 min (once before and 3 times after drug administration) during the 5-day drug-administration period, and continued once a day until 8 days after the final administration. The antiepileptic effects of 5-day administration of conventional AEDs (PHT, PB, VPA, and CBZ) were examined by using similar methods.
RESULTS:Tonic convulsions and absence-like seizures were inhibited by a single administration of LEV at 80 and 160 mg/kg, i.p., but not significantly at 40 mg/kg, i.p. When LEV was repeatedly administered at 80 mg/kg/day, i.p., for 5 days to SERs, the inhibitory effects on seizures increased with administration time. The number of tonic convulsions and absence-like seizures were significantly reduced to 39.1% and 38.4% compared with previous values, respectively, after 5-day LEV administration. Furthermore, significant inhibition of tonic convulsions was detected CONCLUSIONS:These results show that LEV is effective in the treatment of both convulsive and absence-like seizures in SERs after single- and multiple-dose administration. Interestingly, in the 5-day administration study, it was found that the antiepileptic effects for tonic convulsions and absence-like seizures were observed both during the drug-administration period and
Volume 46(9)
Pages 1362-70
Published 2005-9
DOI 10.1111/j.1528-1167.2005.29604.x
PII EPI29604
PMID 16146430
MeSH Animals Anticonvulsants / pharmacology* Behavior, Animal / drug effects Cerebral Cortex / drug effects Cerebral Cortex / physiopathology Disease Models, Animal Dose-Response Relationship, Drug Electroencephalography / drug effects Epilepsy / physiopathology Epilepsy / prevention & control* Epilepsy, Absence / physiopathology Epilepsy, Absence / prevention & control* Epilepsy, Generalized / physiopathology Epilepsy, Generalized / prevention & control Female Injections, Intraperitoneal Levetiracetam Male Piracetam / analogs & derivatives* Piracetam / pharmacology Rats Rats, Mutant Strains Time Factors
IF 5.562
Times Cited 40
Rats SER/Kyo(strainID=28)