Interaction between phenytoin and diazepam in mutant Han-Wistar rats with progressive spastic paresis.

The muscle relaxant (antispastic) effect of diazepam, alone or in combination with phenytoin, was studied in mutant Han-Wistar rats with progressive spastic paresis. Alone, phenytoin did not alter the spontaneous activity in the electromyogram (EMG) of the gastrocnemius soleus (GS) muscle of mutant rats, but strongly enhanced the depressant action of diazepam on the spontaneous EMG activity. Picrotoxin reduced the antispastic effect of diazepam alone and partially reversed the antispastic effect of combined treatment. Therefore, the antagonistic effect of picrotoxin on the reduction of the spontaneous activity in the EMG produced by the combination of both drugs hardly suggests an interaction of picrotoxin with phenytoin, but rather indicates an interaction with the effect of diazepam. Phenytoin enhancement of the depressant action of diazepam on the spontaneous EMG activity of mutant rats strongly suggests the potential therapeutic usefulness of the combined treatment with both drugs.