Copyright © 2008 Published by Elsevier B.V.
Pharmacokinetics, safety, and tolerability of the new antiepileptic carisbamate in the elderly
Carisbamate produced a dose-dependent reduction in photosensitivity in the 13 evaluable patients, with abolishment of photoparoxysmal responses in 3 patients and clinically significant suppression of such responses in 7 additional patients. Photosensitivity was abolished or reduced in all five patients in the 1000-mg dose group. The onset of carisbamate occurred rapidly, with clinically significant suppression achieved before or near the time peak plasma drug levels were reached. The duration of action was dose-related and long-lasting, with clinically significant reductions of photosensitivity observed for up to 32 h after doses of 750 or 1000 mg. Carisbamate was generally well tolerated, with dizziness and nausea reported more frequently after active drug than placebo.
This study shows that carisbamate exhibits dose-related antiepileptic effects in the photosensitivity model. Randomized, controlled studies of carisbamate in epilepsy patients inadequately controlled by their existing AED therapy are warranted.
gn="top" style="padding: 5px 5px 0px 5px"> | gUdi=B6T34-4RV1JSP-2&_fmt=high&_coverDate=05%2F31%2F2008&_rdoc=1&_orig=article&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=0152e1ff45e60f4518867014967000a2" onMouseOver="InfoBubble.show('infobubble_3','mlktLink_3')" onMouseOut="InfoBubble.timeout()">The novel antiepileptic drug carisbamate (RWJ 333369) i... Epilepsy Research |
ght; padding-left:5px"> Epilepsy Research, Volume 79, Issues 2-3, May 2008, Pages 158-165 Laxmikant S. Deshpande, Nisha Nagarkatti, Sompong Sombati, Robert J. DeLorenzo Abstract ght:150%"> SummaryThis study was initiated to investigate effects of the novel neuromodulator carisbamate (RWJ 333369) in the hippocampal neuronal culture model of status epilepticus and spontaneous epileptiform discharges. Whole-cell current clamp techniques were used to determine the effects of carisbamate on spontaneous recurrent epileptiform discharges (SREDs, in vitro epilepsy), depolarization-induced sustained repetitive firing (SRF) and low Mg2+-induced continuous high frequency spiking (in vitro status epilepticus). This in vitro model is an important tool to study the effects of anticonvulsant drugs (AEDs) on SREDs that occur for the life of the neurons in culture. Carisbamate dose dependently blocked the expression and reoccurrence of SREDs. The ED50 value for its antiepileptic effect was 58.75 ± 2.43 μM. Inhibition of SRF is considered a common attribute of many AEDs. Carisbamate (100 μM) significantly decreased SRF in hippocampal neurons. All these effects of carisbamate were reversed during a 5 to 30 min drug washout period. When exposed to low Mg2+ medium cultured hippocampal neurons exhibit high frequency spiking. This form of in vitro status epilepticus is not effectively blocked by conventional AEDs that are known to be effective in treating status epilepticus in humans. Carisbamate, like phenytoin and phenobarbital, had little or no effect on low Mg2+-induced continuous high frequency spiking. These results characterize the effects of carisbamate in the hippocampal neuronal culture model of epileptiform discharges and suggest that the ability of carisbamate to inhibit depolarization-induced SRF may account in part for some of it's anticonvulsant effect.g&_imagekey=B6T34-4S32DJ3-1-F&_cdi=4936&_user=10&_orig=article&_coverDate=05%2F31%2F2008&_sk=999209997&view=c&wchp=dGLbVzW-zSkWA&md5=5f58c26ebb112735a90891acac31d4a1&ie=/sdarticle.pdf"> |
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Pharmacokinetics, safety, and tolerability of the new antiepileptic carisbamate in the elderly