Benzodiazepine cross-tolerance in mice extends to sodium valproate

Slow intravenous infusion of pentylenetetrazol was used to measure the convulsive threshold in mice. The anticonvulsant effects of clobazam, clonazepam, diazepam, lorazepam, sodium phenobarbitone and sodium valproate were assessed in naive animals and compared with the effects of the same compounds in animals which had been pretreated (twice daily for 3 days) with one of the benzodiazepines or sodium valproate. Cross-tolerance was observed between all the benzodiazepines but not between benzodiazepines and sodium phenobarbitone. Animals pretreated with the benzodiazepines were cross-tolerant to valproate, but the converse was not true; nor did sodium valproate induce tolerance to itself.