Organophosphates essentially irreversibly inhibit acetylcholinesterase by leaving a phosphate group bound to the enzyme. Oximes, such as pralidoxime, reversibly bind to acetylcholinesterase and have high affinity for binding to phosphate groups. They can, therefore, bind to acetylcholinesterase, pick up the phosphate group inhibiting the acetylcholinesterase, and take the phosphate group with them when they leave the acetylcholinesterase. Thus pralidoxime can be used to regenerate acetylcholinesterase after organophosphate poisoning.

A limitation of pralidoxime is that it is only effective in a limited time window before ageing of the organophosphate inhibition of acetylcholinesterase occurs. Pralidoxime itself binds to and competitively inhibits acetylcholinesterase. Therefore, if pralidoxime is administered after all the organophosphate-inhibited acetylcholinesterase has already aged, pralidoxime will just make the anticholinesterase poisoning worse. It is therefore important to administer pralidoxime in the appropriate time window.

So what is the time window before ageing of the acetylcholinesterase occurs? This is still a matter of some debate in the literature because the sporadic nature, idiosyncratic variability, and severity of organophosphate poisoning events make conduction of clinical trials challenging. However, based on studies of ageing of acetylcholinesterase in erythrocytes in vitro the time window is thought to be different depending on the nature of the organophosphate. For dimethylphosphorylation by organophosphates such as malathion, the half-life for ageing of acetylcholinesterase is estimated to be 3.7 hours on average (Eddleston, 2002; Worek et al., 1997; Worek et al., 1999). Therefore, in the case of poisoning with malathion, it would be preferable to administer the pralidoxime within less than 2 to 3 hours, but it would likely be more harmful than helpful to administer the pralidoxime after 13 hours (Bismuth et al., 1992; Eddleston, 2002; Worek et al., 1997).  In contrast, for diethylphosphorylation by organophosphates such as parathion, the window is longer as the half-life for ageing of acetylcholinesterase is on average 33 hours (Eddleston, 2002; Worek et al., 1997; Worek et al., 1999). Therefore, it would be preferable to administer the pralidoxime within less than 20 to 30 hours but the pralidoxime could still be effective up to 132 hours after poisoning (Bismuth et al., 1992; Eddleston, 2002; Worek et al., 1997).

References:

Bismuth C, Inns RH, Marrs TC (1992) Efficacy, toxicity and clinical uses of oximes in anticholinesterase poisoning. In: Ballantyne, B.; Marrs, TC., editors. Clinical and experimental toxicology of organophosphates and carbamates. Butterworth Heinemann; Oxford. p. 555-577.

Eddleston M, Szinicz L, Eyer P, Buckley, N (2002) Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials. QJM. 95(5): 275–283.

Worek F, Backer M, Thiermann H, et al. (1997) Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning. Hum Exp Toxicol. 16: 466–472.

Worek F, Diepold C, Eyer P. (1999) Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation and ageing kinetics. Arch Toxicol. 73: 7–14.