Anticonvulsant activity of flumazenil in rats during ontogenetic development

The influence of flumazenil on seizures induced by pentylenetetrazol (PTZ) was studied in rats aged 7, 12, 18, 25, and 90 days. Flumazenil in doses of 25, 37.5, and 50 mg/kg IP injected 10 min before PTZ exhibited a dose-dependent anticonvulsant action in all age groups studied. It was more effective against generalized tonic-clonic than against minimal clonic seizures at all developmental stages studied. In the two youngest groups, minimal seizures were elicited only rarely under control conditions. Pretreatment with the two lower doses of flumazenil resulted in an increased incidence of this type of seizure for these two groups. The anticonvulsant activity found in all age groups is in agreement with data from other benzodiazepines and speaks against a pure benzodiazepine-antagonistic action of flumazenil.