The effects of carisbamate on the thalamic metabolism of [1-13C]glucose and [1,2-13C]acetate in the lithium-pilocarpine rat model

Abstract

Temporal lobe epilepsy is the most common type of epilepsy, the latter which has a worldwide occurrence of approximately 1%. As it is also a highly intractable disease, there is a pressing need for the development or improvement of antiepileptic drugs. In this study, the thalamic metabolism in lithium-pilocarpine-treated rats with chronic temporal lobe epilepsy was examined. Additionally, in a previous study, the rats of the same animal model had developed either temporal lobe epilepsy or absence-like epilepsy when treated with the novel antiepileptic drug carisbamate (CRS; RWJ 333369; S-2-O-carbamoyl-1-O-chlorophenyl-ethanol). The metabolic effects of carisbamate on the thalamus of these rats were therefore investigated. In both cases, this was done by using high performance liquid chromatography and nuclear magnetic resonance spectroscopy.

The results found include a disturbed neuronal metabolism in the thalamus of rats with chronic temporal lobe epilepsy, which may be due to either neuronal loss or impaired TCA cycle activity. Furthermore, the treatment with carisbamate was found to have normalising effects on the neuronal metabolism, thus indicating that this drug is neuroprotective. Finally, the metabolic differences between the rats that developed temporal lobe and absence-like epilepsy were limited to a lower level of GABA for the latter. Although the reason for this is not apparent, it may reflect the opposing effects GABA has on the regulation of seizures in the two epilepsy types.