SULFONYL FLUORIDES AND THE PROMOTION OF DIISOPROPYL FLUOROPHOSPHATE NEUROPATHY

Phenylmethanesulfonyl fluoride (PMSF) enhances the neuropathic respons e when given to hens after organophosphates causing delayed polyneurop athy. This study was undertaken to ascertain whether other sulfonyl fl uorides promote diisopropyl fluorophosphate (DFP) neuropathy in hens a nd if they inhibit neuropath, target esterase (NTE), the target for or ganophosphate-induced delayed polyneuropathy. Among seven sulfonyl flu oride analogs of PMSF (alkyl-, and phenylsulfonyl fluorides), only n-b utanesulfonyl fluoride was found to be an NTE inhibitor in vitro at a concentration (I-50 = 60 mu M) similar to that of PMSF. n-Butanesulfon yl 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 o rganophosphate polyneuropathy are also NTE inhibitors. (C) 1996 Societ y of Toxicology