Effects of physostigmine on benzodiazepine toxicity.

The interactions between physostigmine and chlordiazepoxide, diazepam, flurazepam were experimentally evaluated in rats and mice by the following test: loss of righting reflex (LRR), acute toxicity, cardiovascular toxicity and EEG pattern. Physostigmine did not modify the duration of LRR produced by chlordiazepoxide. Conversely, the recovery after diazepam was significantly longer. The LD50 of diazepam and chlordiazepoxide were not modified by physostigmine administration, but that of flurazepam was significantly decreased. Heart rate and blood pressure did not change significantly with physostigmine pre-treatment. However, the total lethal dose was lowered for chlordiazepoxide and flurazepam. Only the reversal by physostigmine of the EEG pattern due to benzodiazepines, offers experimental support to the claimed usefulness of physostigmine in benzodiazepine intoxication in humans. Furthermore, the potentiation of flurazepam toxicity must be taken into account in the debate concerning the clinical advantages of physostigmine.