Increased anticonvulsant effect of phenytoin in aging BDF1 mice

The anticonvulsant effect of phenytoin was examined in BDF1 mice of both sexes and various ages (6, 12, 24 and 30 months old) using the abolition of the tonic hindlimb extensor component of maximal electroshock seizure as the index. The minimal effective plasma concentration of phenytoin was significantly lower in 24- and 30-month-old mice compared with young adult (6 month old) mice. Similarly, all older groups (24 and 30 month old, both sexes) showed significantly lower minimal effective brain concentrations compared with respective younger (6 and 12 month old) animal groups. Studies using nearly 2-fold different intensities of electroshock (30 and 55 mA) showed almost identical results. The results provide evidence that, in adult mice, the brain becomes more sensitive with age to phenytoin with regard to its anticonvulsant effect.