MODIFICATION OF THE RATE OF AGING OF DIISOPROPYLFLUOROPHOSPHATE-INHIBITED NEUROPATHY TARGET ESTERASE OF HEN BRAIN

This study was aimed to investigate the possibility of modifying the r ate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of hen blain. This reaction on NTE occurs with a half- time of 7.4 min. Atropine was effective in decreasing the rate of agin g on DFP-inhibited NTE and this effect was time-and concentration-depe ndent. Atropine was also a weak but progressive inhibitor of NTE activ ity (I-50 = 80 mM) and this reaction appears to be reversible at lower atropine concentrations. Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophy lic than other oximes usually used in acetylcholinesterase (AChE) reac tivation studies, was effective in decreasing the rate of aging on DFP -inhibited NTE. However, when atropine and oximes were used together w e have obtained a potentiating and/or synergistic effect which was mos t significant with combination of atropine and TMB-4 giving up to a 15 -fold decrease in the rate of aging reaction. The efficacy of this par ticular combination was concentration-dependent. We have also discusse d similarities and differences in aging reaction occurring on NTE and AChE. (C) 1998 Elsevier Science Inland Ltd. All rights reserved.