Felbamate in experimental model of status epilepticus.
OBJECTIVE
To examine the putative seizure-protective properties of felbamate in an animal model of self-sustaining status epilepticus (SSSE).


METHODS
SSSE was induced by 30-min stimulation of the perforant path (PPS) through permanently implanted electrodes in free-running male adult Wistar rats. Felbamate (FBM; 50, 100, and 200 mg/kg), dizepam (DZP; 10 mg/kg), or phenytoin (PHT; 50 mg/kg) were injected i.v. 10 min after SSSE induction. Electrographic manifestations of SSSE and the severity of SSSE-induced neuronal injury were analyzed.


RESULTS
Felbamate injected during the early stages of SSSE (10 min after the end of PPS), shortened the duration of seizures in a dose-dependent manner. Total time spent in seizures after FBM and 290 +/- 251 min (50 mg/kg), 15.3 +/- 9 min (100 mg/kg), and 7 +/- 1 min (200 mg/kg), whereas control animals spent 410 +/- 133 min seizing. This effect of FBM was stronger than that of DZP (10 mg/kg, 95 +/- 22 min) and comparable to that of PHT (50 mg/kg, 6.3 +/- 2.5 min). In the applied doses, FBM (200 mg/kg) was more effective than PHT (50 mg/kg) or DZP (10 mg/kg) in shortening seizure duration and decreasing spike frequency, when administered on the pleateau of SSSE (injection 40 min after the end of PPS). Anticonvulsant action of FBM was confirmed by milder neuronal injury compared with control animals.


CONCLUSIONS
Felbamate, a clinically available AED with a moderate affinity for the glycine site of the NMDA receptor, displayed a potent seizure-protective effect in an animal model of SSSE. These results suggest that FBM might be useful when standard AEDs fail in the treatment of refractory cases of SE.
Mazarati
A M
AM
Greater Los Angeles Health Care System, Sepulveda 91343-2099, California, USA. mazarati@ucla.edu
Baldwin
R A
RA
Sofia
R D
RD
Wasterain
C G
CG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D000078328:Felbamate; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019580:Perforant Pathway / Q000187:drug effects / Q000503:physiopathology; D048448:Phenylcarbamates; D010672:Phenytoin / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013226:Status Epilepticus / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D010672:Phenytoin; D003975:Diazepam; D000078328:Felbamate