Folic acid and the protective action of diphenylhydantoin against maximal electroshock in rats after single doses

Conflicting evidence regarding the antagonistic action of folic acid (FA) on the efficiency of the antiepileptic drug diphenylhydantoin (DPH) led us to study this problem in rats. From the results it is concluded that the enteral absorption of particularly higher doses of DPH is slightly hampered by FA. When the dose of DPH is high enough, this diminished absorption will not manifest itself in impaired protection. On the basis of DPH levels in brain tissue it is concluded that also on brain level there is some antagonistic action of FA on DPH protection. Here too, a sufficiently high level of DPH prevents this antagonistic action from becoming evident. We suggest that only in patients in whom the DPH treatment is marginal, FA treatment may hamper the therapeutic antiepileptic effect.