Sulfonyl Fluorides and the Promotion of Diisopropyl Fluorophosphate Neuropathy

Phenylmethanesulfonyl fluoride (PMSF) enhances the neuropathic response when given to hens after organophosphates causing delayed polyneuropathy. This study was undertaken to ascertain whether other sulfonyl fluorides promote diisopropyl fluorophosphate (DFP) neuropathy in hens and if they inhibit neuropathy target esterase (NTE), the target for organophosphate-induced delayed polyneuropathy. Among seven sulfonyl fluoride analogs of PMSF (alkyl-, and phenylsulfonyl fluorides), only n-butanesulfonyl fluoride was found to be an NTE inhibitor in vitro at a concentration (I50=60 μM) similar to that of PMSF. n-Butanesulfonyl fluoride (0.2 mmol·kg−1 sc to hens) caused both NTE inhibition in nervous tissues (>80%) and promotion of neuropathy after DFP (0.003 mmol·kg−1 sc) similar to those observed after the same molar dose of PMSF. These results confirm that, so far, all known promoters of organophosphate polyneuropathy are also NTE inhibitors.