Effect of combined treatment of diphenylhydantoin with clonazepam and chlordiazepoxide on the threshold for maximal electroconvulsions in mice.

The anticonvulsant effect of either clonazepam (0.2-6.4 mg/kg) or chlordiazepoxide (2.5-40 mg/kg) alone or in combination with diphenylhydantoin (4-16 mg/kg) was studied against electroconvulsions in mice. All drugs were injected intraperitoneally, diphenylhydantoin - 75 min and the benzodiazepines - 60 min before the test. Adding either clonazepam or chlordiazepoxide (in doses moderately increasing the convulsive threshold) was more effective than doubling the dose of diphenylhydantoin. Both the interaction between benzodiazepines and diphenylhydantoin at the level of the receptor for picrotoxin-barbiturates and benzodiazepine-induced potentiation of specific diphenylhydantoin binding are likely to contribute to the observed phenomenon. On the other hand, a diphenylhydantoin-induced increase in the total number of specific benzodiazepine binding sites seems of minor importance since clonazepam (with a high affinity for these sites) and chlordiazepoxide (with a low affinity) were equipotent in the enhancement of the combined treatment efficacy.