The conjoined poison / antidote then unbinds from the site, and thus regenerates the fully functional enzyme.

Some phosphate-acetylcholinesterase conjugates continue to react after the phosphate docks to the esteric site, evolving into a more recalcitrant state.

It may have limited beneficial effects if the acetylcholinesterase enzyme is carbamylated, as occurs with neostigmine, pyridostigmine, or insecticides such as carbaryl.

The following precautions should be kept in mind in the treatment of anticholinesterase poisoning, although they do not bear directly on the use of pralidoxime: since barbiturates are potentiated by the anticholinesterases, they should be used cautiously in the treatment of convulsions; morphine, theophylline, aminophylline, succinylcholine, reserpine, and phenothiazine-type tranquilizers should be avoided in patients with organophosphate poisoning.

Relative contraindications include known hypersensitivity to the drug and other situations in which the risk of its use clearly outweighs possible benefit.