Folate Metabolism and the Anticonvulsant Efficacy of Phenobarbital

Because of reports that therapeutic administration of folate sodium may be associated with an exacerbation of seizures in some epileptic patients, the relationship of folate and vitamin B12 plasma levels with seizure threshold as well as the anticonvulsant efficacy of phenobarbital were examined in albino rats. Seizures were induced with the volatile convulsant flurothyl. Chronic administration of phenobarbital was found to be associated with relative reduction of plasma folate levels in all animals. In contrast, vitamin B12 levels were unaffected. Under these experimental conditions, low plasma folate levels were associated with an enhanced anticonvulsant effectiveness of phenobarbital when seizure threshold was measured to the beginning of a tonic-clonic seizure, while dietary supplementation with folate apparently reduced the effectiveness of phenobarbital in raising this measure of the seizure threshold. Plasma vitamin B12 levels did not affect the seizure threshold elevation produced by phenobarbital.