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

The toxicity of hyperbaric oxygen in the central nervous system is expressed by generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested flunarizine, a calcium antagonist known to have antiepileptic properties and only minimal cardiovascular side effects. 49 rats with chronic cortical electrodes were injected i.p. with six different doses of flunarizine (10-300 mg/kg) or vehicle, before exposure to 0.5 MPa oxygen. Two doses of flunarizine and vehicle were given to rats exposed to oxygen with 5% CO2 at an absolute pressure of 0.5 MPa. EEG and spectral analysis of background EEG activity were monitored. The duration of the latent period before the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. There was no statistical difference between the duration of the latent periods for the seven groups treated by flunarizine or by vehicle on exposure to 0.5 MPa pure oxygen (P = 0.9 in ANOVA), but on exposure to oxygen with CO2, there was significant prolongation of the latent periods in comparison with vehicle (P < 0.001). Our results suggest that on exposure to hyperbaric oxygen, the antiepileptic effect of flunarizine might be masked, probably by its cerebral antivasoconstrictive effect.