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- W2034692577 abstract "Abstract At 37°C and pH 8.0 the resolved isomers of S-(4-chlorobenzyl or 2,4-dichlorobenzyl) ethyl phenylphosphonothiolate are moderate inhibitors of AChE of hen brain (ka = 300−1400 M−1min−1) and weak inhibitors of neuropathy target esterase (NTE) (ka = 40−240 M−1min−1). The two (R)P(+) isomers are more active against NTE than are the (S)P(−) while the opposite is true for AChE. NTE inhibited by either (R)P(+) isomer underwent slow spontaneous reactivation (about 30% in 18 hr) but (S)P(−)-inhibited NTE did not reactivate. No spontaneous reactivation was detected for AChE inhibited by either steric form. AChE inhibited by (R)p(+) isomers could be reactivated by N-methylpyridinium-2-aldoxime methanesulfonate and slow aging was detected (23% in 18 hr). NTE inhibited by (R)p(+) isomers could be reactivated by ω-isonitrosoacetophenone and no significant aging occurred in 18 hr at 37°C. Neither of the enzymes could be reactivated 60 min after commencement of inhibition with saturated solutions of the (S)p(−) isomers. NTE inhibited by racemic EPNO in a 1-min incubation formed a mixture of rapidly aging ( t 1 2 ⋍ 1 min ) and apparently non-aging inhibited NTE. Since EPNO should form the same ethyl phenylphosphonylated enzymes as the isomers under study we conclude that the oxime-resistance of inhibited NTE after inhibition by these (S)p(−)-isomers is due to rapid formation of aged enzyme during the (necessarily) long inhibition period. Substantial inhibition of NTE in vivo should be possible in hens protected against cholinergic effects of a dose of either (R)P(+) isomer. The toxicological consequence of such inhibition (? neuropathy or protection) should be investigated." @default.
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- W2034692577 date "1986-02-01" @default.
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- W2034692577 title "The effect of steric factors on the interaction of some phenylphosphonates with acetylcholinesterase and neuropathy target esterase of hen brain" @default.
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- W2034692577 doi "https://doi.org/10.1016/0048-3575(86)90040-4" @default.
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