Pharmaco-EEG-based assessment of interaction between ethanol and levetiracetam

Abstract

Recent research suggests a potential role for a new generation of anticonvulsant drugs, including levetiracetam, in the treatment of alcohol dependence. Some elements of the central mechanism of action that levetiracetam has in common with ethanol, give rise to the question of whether there is an interaction between these two agents and whether there is any risk associated with the enhanced depressive effect of these agents on the central nervous system. In this study, we have used a pharmaco-electroencephalographic (EEG) method to examine the interaction of ethanol with levetiracetam. The influence of levetiracetam on the effect of ethanol on EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex) was determined. Levetiracetam was administered p.o. as a single dose (50 mg/kg or 200 mg/kg) or repeatedly at a dose of 100 mg/kg/day for 14 days. Ethanol was injected i.v. at a dose of 0.8 g/kg 60 min after the administration of levetiracetam. Ethanol caused an increase in the low frequencies (0.5–4 Hz) in the recording, as well as a marked decrease in the higher frequencies (13–30 Hz and 30–45 Hz). Changes in the EEG recordings after levetiracetam alone were more significant when the drug was given in repeated doses. Combined administration of ethanol and levetiracetam (200 mg/kg) resulted in a markedly synergistic effect in the frontal cortex and the midbrain reticular formation. The drug decreases the sensitivity of the hippocampus to ethanol, an observation that may be important in the treatment of alcohol addiction.