Interactions of cholinesterase inhibitors and corticosteroids with the hypnotic effect of benzodiazepines in mice.

Interactions of cholinesterase inhibitors or dexamethasone with the hypnotic effect of benzodiazepines appear to be strongly dependent on the dose of the cholinesterase inhibitor used and to a lesser extent on the dose of the hypnotic. The duration of the loss of righting reflex caused by the benzodiazepines, diazepam or chlorodiazepoxide, is markedly prolonged by 500 micrograms/kg, significantly antagonized both diazepam and chlorodiazepoxide. Relatively higher doses of physostigmine have no significant effect on either diazepam or chlorodiazepoxide. Dexamethasone, in relatively low doses of 250 and 500 micrograms/kg or 500 micrograms/kg respectively, significantly reverses the effect of diazepam and chlorodiazepoxide, while in relatively high doses of 1000 micrograms/kg the hormone significantly potentiates the hypnosis produced by the benzodiazepines. It is suggested that the interactions described may be the result of a modification of possible changes in cholinergic activity caused by the benzodiazepines. Although as yet no unequivocal explanation can be offered for the different effects, the observations described in this paper may explain the highly contradictory findings of other authors in both animal and human studies.