rwj-333369 and Epilepsy--Reflex

Carisbamate, a novel neuromodulatory agent with antiepileptic properties, was evaluated in patients with photoparoxysmal responses to intermittent photic stimulation (IPS) in this multicenter, non-randomized, single-blind, placebo-controlled, proof-of-concept study.. Eighteen Caucasian patients (14 females, 4 males) with a mean age of 30 years (range: 16-51 years) underwent standardized IPS under three eye conditions (during eye closure, eyes closed and eyes open) at hourly intervals for up to 8h after receiving placebo (Day 1), carisbamate (Day 2) and placebo (Day 3). Carisbamate was given at single doses of 250-1000 mg. All patients received one or two concomitant antiepileptic drugs, most commonly valproate.. 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.

Topics: Adolescent; Adult; Affect; Anticonvulsants; Carbamates; Depression; Dose-Response Relationship, Drug; Epilepsy, Reflex; Female; Humans; Male; Middle Aged; Photic Stimulation; Psychiatric Status Rating Scales

The antiepileptic effects of carisbamate were assessed in two models of genetic epilepsy, a model of absence seizures, the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and a model of convulsive seizures, the Wistar Audiogenic Sensitive (AS) rat.. GAERS were equipped with four cortical electrodes over the frontoparietal cortex and the duration of spike-and-wave discharges (SWD) was recorded for 20-120 min. In Wistar AS, the occurrence of, latency to, and duration of wild running and tonic seizures were recorded.. In GAERS, carisbamate (10, 30, and 60 mg/kg) dose dependently reduced the expression of SWD that totally disappeared at the two highest doses by 40 min after injection. SWD duration returned to control levels by 100 min after the injection of 30 mg/kg carisbamate while SWDs were totally suppressed for 120 min after the injection of 60 mg/kg carisbamate. In Wistar AS, 10 mg/kg carisbamate increased the latency to the first running episode and induced the occurrence of a second running episode in three of eight rats. This episode was not present in untreated rats and was indicative of decreased sensitivity to the stimulus. This dose of carisbamate increased by 327% the latency to the tonic seizure that still occurred in the six of eight rats studied. At 20 and 30 mg/kg, no rats exhibited any wild running or tonic seizure.. The present results support the broad spectrum of antiepileptic activity of carisbamate confirming its efficacy in animal models of primary generalized seizures of both tonic-clonic and of the absence type.

Topics: Animals; Anticonvulsants; Behavior, Animal; Carbamates; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Absence; Epilepsy, Generalized; Epilepsy, Reflex; Frontal Lobe; Fructose; Male; Motor Activity; Parietal Lobe; Rats; Rats, Wistar; Reaction Time; Species Specificity; Topiramate