Effects of combined treatment with diphenylhydantoin and different benzodiazepines on pentylenetetrazol- and bicuculline-induced seizures in mice.

The anticonvulsant effects of clonazepam, nitrazepam and chlordiazepoxide alone, or combined with diphenylhydantoin, were studied on pentylenetetrazol- and bicuculline-induced seizures. Diphenylhydantoin remained without influence upon the chemically induced convulsions but potentiated the antipentylenetetrazol activity of clonazepam and nitrazepam. Also, the combination of diphenylhydantoin and clonazepam resulted in a distinct decrease in the ED50 value of the latter drug against the tonic (but not the clonic) phase of bicuculline-induced seizures. On the other hand, diphenylhydantoin did not enhance the anticonvulsant activity of chlordiazepoxide against both convulsants used nor did it affect the protective action of nitrazepam against bicuculline. The suggestion is made that a diphenylhydantoin-induced increase in the total number of specific benzodiazepine receptors might be of importance for the potentiation of the antipentylenetetrazol effects of some benzodiazepines. The interaction between diphenylhydantoin and clonazepam seems to be more complex and probably involves other mechanisms.