Carisbamate prevents the development and expression of spontaneous recurrent epileptiform discharges and is neuroprotective in cultured hippocampal neurons.
OBJECTIVE
Although great advances have been made in the development of treatments for epilepsy, acquired epilepsy following brain injury still comprises approximately 50% of all the cases of epilepsy. Thus, development of drugs that would prevent or decrease the onset of epilepsy following brain injury represents an important area of research.


METHODS
Here, we investigated effects of carisbamate (RWJ 333369) on the development and expression of spontaneous recurrent epileptiform discharges (SREDs) and its neuroprotective potential in cultured hippocampal neurons. This model utilizes 3 h of low Mg(2+) treatment to mimic status epilepticus (SE-like) injury in vitro. Following the injury, networks of neurons manifest synchronized SREDs for their life in culture. Neuronal cultures were treated with carisbamate (200 microM) for 12 h immediately after the SE-like injury. The drug was then removed and neurons were patch clamped 24 h following drug washout.


RESULTS
Treatment with carisbamate after neuronal injury prevented the development and expression of epileptiform discharges. In the few neurons that displayed SREDs following carisbamate treatment, there was a significant reduction in SRED frequency and duration. In contrast, phenytoin and phenobarbital, when used in place of carisbamate, did not prevent the development and expression of SREDs. Carisbamate was also effective in preventing neuronal death when administered after SE-like injury.


CONCLUSIONS
Carisbamate prevents the development and generation of epileptiform discharges and is neuroprotective when administered following SE-like injury in vitro and may offer a novel treatment to prevent the development of epileptiform discharges following brain injuries.
Deshpande
Laxmikant S
LS
Department of Neurology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Nagarkatti
Nisha
N
Ziobro
Julie M
JM
Sombati
Sompong
S
DeLorenzo
Robert J
RJ
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004827:Epilepsy / Q000503:physiopathology / Q000517:prevention & control*; D006624:Hippocampus / Q000166:cytology*; D008274:Magnesium / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; D008274:Magnesium; D010634:Phenobarbital