Paraoxon Reversibly Inhibits Neurotoxic Esterase

It has recently been reported that two paraoxon-insensitive carboxylesterases may be distinguished by their sensitivity to mipafox. However, we have not been able to reliably detect two components under the conditions of the widely used assay for neurotoxic esterase (NTE). We have determined that this discrepancy is a result of differences in the technique of preinhibition by paraoxon and mipafox. We report here that paraoxon is apparently able to reduce the rate of inhibition of both neurotoxic esterase isozymes by mipafox in a concentration-dependent manner. As a result, the rate of inhibition of NTE by mipafox is greater when sequential, rather than concurrent, preinhibition is utilized. An apparently greater reduction in the inhibition rate of the more sensitive minor component may make the two isozyme species indistinguishable in the presence of paraoxon at concentrations at or above 40 microM.