Interaction of diphenhydramine with cholinesterase inhibitors in mice.

Physostigmine (1.5 mg/kg, s.c.) and neostigmine (1.0 mg/kg, s.c.) injection into male mice produced signs of toxicosis characteristic of cholinesterase inhibition and evoked death in 95 and 94% of the animals respectively. Diphenhydramine injections (5-30 mg/kg, s.c.) 15 min before physostigmine or neostigmine significantly increased the latency period to onset of death and the percentage of survivors. Diphenhydramine injection (20 mg/kg, s.c.) between -30 and +2 min (but not at +5 and +10 min) relative to physostigmine prevented lethality in 100% of the animals. The data indicated that diphenhydramine which possesses anticholinergic effects protected mice against physostigmine- and neostigmine-induced toxicosis.