Anticonvulsant and antiepileptogenic effects of fluorofelbamate in experimental status epilepticus.
OBJECTIVE
To examine the seizure-protective properties of fluorofelbamate, a felbamate analog, on acute and chronic seizures in an experimental model of self-sustaining status epilepticus (SSSE).


METHODS
SSSE was induced by stimulation of the perforant path for 30 min (PPS) through chronically implanted electrodes in free-running adult male Wistar rats. Fluorofelbamate was injected intravenously (i.v.) either 10 min, or 40 min after SSSE induction. Seizure and spike profiles were analyzed off-line.


RESULTS
Fluorofelbamate injected during the early stages of SSSE (10 min after the end of PPS), shortened the duration of seizures in a dose-dependent manner. While a dose of 50 mg kg(-1) was ineffective, 100 and 200 mg kg(-1) reduced cumulative seizure time from 393 +/- 10 min to 15 +/- 8 min and 2.4 +/- 0.5 min respectively. Administration of fluorofelbamate (200 and 300 mg kg (-1)) at a late stage of SSSE, which is refractory to treatment with conventional anticonvulsants, also significantly attenuated seizures. Acute fluorofelbamate treatment (200 mg kg(-1) 10 min after PPS) significantly decreased the frequency of spontaneous seizures which follow SSSE after a 'latent' interval. Moreover, in contrast to control animals, fluorofelbamate-treated rats showed regression of spontaneous seizures, and an apparent remission of epilepsy within 2 months after SSSE.


CONCLUSIONS
Acute treatment of SSSE with fluorofelbamate showed strong anticonvulsant effects even during the late stages of SSSE. In this model, it also displayed antiepileptogenic properties: it reduced the severity of chronic epilepsy after SSSE and lead to apparent remissions of that epilepsy.
Mazarati
Andrey M
AM
Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
Sofia
R Duane
RD
Wasterlain
Claude G
CG
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002908:Chronic Disease; D004567:Electrodes, Implanted; D004569:Electroencephalography; D000078328:Felbamate; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012074:Remission Induction; D013226:Status Epilepticus / Q000175:diagnosis / Q000188:drug therapy*
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate