The effect of vigabatrin on central nervous system oxygen toxicity in rats

The toxicity of hyperbaric oxygen in the central nervous system is expressed by clinical and electroencephalographic (EEG) manifestations resembling those of generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested vigabatrin, an irreversible inhibitor of GABA (gamma-aminobutyric acid) transaminase. Five different doses of vigabatrin (ranging from 50 to 500 mg/kg) or vehicle were injected i.p. in rats implanted with cortical electrodes, 4 h prior to exposure to 5 ATA (0.5 MPa) oxygen. EEG and spectral analysis of the background EEG activity were monitored for the different dosages of the drug. The duration of the latent period before the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. The protective effect of vigabatrin was dose-related, and complete protection against hyperoxic-induced discharges was at 180 mg/kg. The protective effect lasted 24 h and decreased gradually disappearing completely on the third day. An increase in the low frequency bands of the EEG and a decrease in the faster activity were correlated with the vigabatrin dosage injected. Our results suggest that vigabatrin has the potential of being a useful drug in the treatment and prevention of oxygen-induced seizures during hyperbaric oxygen therapy.