Mipafox delayed neuropathy

A few OP compounds cause delayed neuropathy in vertebrates because they inhibit another esterase located in the nervous system, which has been termed neuropathy target esterase (NTE). This enzyme is described in Chapter 10, Section 10.2.4. OPs that cause delayed neuropathy include diisopropyl phosphofluoridate (DFP), mipafox, leptophos, methamidophos, and triorthocresol phosphate. The delay in the appearance of neurotoxic symptoms following exposure is associated with the aging process. In most cases, nerve degeneration is not seen with initial inhibition of the esterase but appears some 2-3 weeks after commencement of exposure, as the inhibited enzyme undergoes aging (see Section 16.4.1). The condition is described as OP-induced delayed neuropathy (OPIDN). 

Neuropathy target esterase (NTE) An esterase of the nervous system whose inhibition by certain OPs (e.g., mipafox, leptophos) can lead to the development of delayed neuropathy. 

Carboni, D., Ehrich, M., Dyer, K., and Jortner, B.S., Comparative evolution of mipafox-in-duced delayed neuropathy in rats and hens, Neurotoxicology, 13(4), 723-33,1992. 

Mipafox was developed for insecticidal use but was withdrawn for that application because of its potential for causing delayed neuropathy. It is currently used as a selective inhibitor of NTE. DFP has a common property with mipafox for inducing delayed nemopathy. 

The esterase got the names neurotoxic esterase or neuropathy target esterase, and the ester phenyl valerate (PV) was found to be a good substrate for this esterase. However, PV is also hydrolyzed by other esterases because paraoxon, which does not give symptoms of delayed neurotoxicity, inhibited the PV activity as much as 80%. The NTE is defined as the hydrolytic activity against PV that is not inhibited by paraoxon but by mipafox. About 3% of the activity is not inhibited by mipafox plus paraoxon. Thus, the part of PV activity due to neurotoxic esterase should be 17%. 

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