Interactions of phenytoin with ouabain and other chemical convulsants.

Phenytoin potentiated the convulsive actions of bicuculline and picrotoxin in mice, whereas the action of bemegride was neither potentiated nor antagonized. Seizures induced by intracerebral injection of ouabain were antagonized by phenytoin, as well as by phenobarbital, chlordiazepoxide and valproic acid; trimethadione had a possible small effect, not quite significant at the 5% level; ethosuximide and muscimol did not show significant effects. Seizures induced by intracerebral injection of pentylenetetrazol were antagonized by phenobarbital but not by phenytoin. Tests of phenytoin against other chemical convulsants are reviewed, and it is suggested that phenytoin may be specific for seizures that arise from a derangement of mechanisms involving sodium ions. This strengthens the view that such a derangement is likely in many cases of human epilepsy.