A theoretical kinetic analysis of the protective action exerted by eserine and other carbamate anticholinesterases against poisoning by organophosphorus compounds.

The protection exerted by carbamate anticholinesterases against the lethal effects of organophosphate anticholinesterases is interpreted kinetically. The protective action is shown to depend on the provision (by carbamylation) of a pool of sequestered cholinesterase resistant to organophosphates but which furnishes (by decarbamylation) sufficient active enzyme to essential cholinergic synapses to ensure survival until all free organophosphate is cleared from the tissues. The two main factors governing the extent of protection are the minimum cholinesterase activity compatible with survival and the "enzyme conservation index" defined essentially as the ratio of the rate of enzyme decarbamylation to the rate of enzyme phosphorylation; the lower the "minimum essential cholinesterase" and the higher the "enzyme conservation index", the greater the protection. The theory is shown to be in excellent qualitative agreement with experiment.