Reactivation of phosphorylated AChE does not occur once the enzyme–inhibitor complex has “aged” (Fig. 2). Aging consists in the loss (by nonenzymatic hydrolysis) of one of the two alkoxy (R) groups, and the rate of aging depends on the nature of the alkoxy group (e.g., AChE phosphorylated by an isopropoxy phosphate ages most rapidly). When phosphorylated AChE has aged, the enzyme can be considered to be irreversibly inhibited, and the only means of replacing its activity is through synthesis of new enzyme, a process that could take days.