Certain sulfonates, like
phenylmethanesulfonyl fluoride (PMSF),
carbamates, and phosphinates, when given prior to neuropathic doses of
organophosphates such as diisopropyl phosphorofluoridate (
DFP), protect hens from
organophosphate-induced delayed
polyneuropathy (OPIDP). Protection was related to inhibition of the putative target of OPIDP, which is called
Neuropathy Target Esterase (NTE). NTE inhibition above 70-80% in the nervous system of hens followed by a molecular rearrangement called aging initiates OPIDP. PMSF and other protective chemicals inhibit NTE but OPIDP does not develop because aging cannot occur.
DFP (1 mg/kg sc) inhibited NTE above 70-80% in peripheral nerve and caused OPIDP in hens. Lower doses (0.3 and 0.5 mg/kg sc) caused about 40-60% NTE inhibition and no or marginal OPIDP.
Chlorpyrifos (90 mg/kg po) also caused OPIDP. When repeated (30 mg/kg sc daily for 9 days) or single (5-120 mg/kg sc) doses of PMSF were given after either
DFP or
chlorpyrifos, OPIDP developed in birds treated with nonneuropathic doses of
DFP and was more severe in birds treated with
chlorpyrifos or higher doses of
DFP. PMSF increased NTE inhibition to greater than 90%. Promotion of OPIDP with a single dose of PMSF (120 mg/kg sc) was obtained in birds up to 11 days after a marginally neuropathic dose of
DFP (0.5 mg/kg sc). Promotion was also obtained with phenyl N-methyl N-benzyl
carbamate (40 mg/kg iv) but not with non-NTE inhibitors in vivo such as
paraoxon or benzenesulfonyl
fluoride when given at maximum tolerated doses. These results indicate that protection from OPIDP is only one effect of PMSF because promotion of OPIDP is also observed depending upon the sequence of dosing. Either effect is always related to the doses of PMSF, which inhibit NTE.