Increased anticonvulsant effect of phenobarbital with age in mice--a possible pharmacological index for brain aging

We have recently reported that the anticonvulsant effect of phenytoin increases with age in mice (1). Since some of the mechanisms of anticonvulsant action of phenytoin and phenobarbital may be different, the present study sought to determine whether a similar increase with age in the anticonvulsant effect of phenobarbital could also be observed. The anticonvulsant effect of phenobarbital was examined in BDF1 female mice of different ages (6, 12, 24 and 30 months old) using the abolition of the tonic hindlimb extensor component of maximal electro-shock seizure as the index. The minimal effective concentration (MEC) values of phenobarbital in plasma and brain were significantly lower in aged (24 and 30 month old) mice compared with the respective values in the youngest animal group (6 month old). Series using nearly two-fold different intensities of electroshock (30 and 55 mA) showed almost identical MEC values in 24 month-old mice. It was concluded that the brain of aged mice is more sensitive to phenobarbital, as it is to phenytoin.