Phenyl di-n-pentylphosphinate: a convenient reactivatible inhibitor for studies on neuropathy target esterase (NTE) and protection against organophosphate-induced delayed polyneuropathy.
Phenyl di-n-pentylphosphinate was synthesised by interaction of phenyl phosphorodichloridate and n-pentyl magnesium bromide. The product was purified by silica chromatography (yield 25%). Although much more stable at physiological pH than its 4-nitrophenyl analogue, this ester is a good inhibitor of neuropathy target esterase (NTE): kappa a = 1.7 X 10(5) M-1 min-1. It is a very weak anticholinesterase (kappa a congruent to 10 M-1 min-1). In vivo only 5-10 mg/kg is required to inhibit hen brain and spinal cord NTE. The inhibited NTE can be reactivated fully by incubation in vitro with iso-nitrosoacetophenone (INAP) (19 mM at 37 degrees C and pH 8.5 for 60 min): this property enables study to be made of the fate of inhibited NTE in vivo.
Johnson
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MK
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
Bird
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Meredith
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D000818:Animals; D001921:Brain / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002645:Chickens; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D009422:Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control*; D013116:Spinal Cord / Q000201:enzymology; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; C057114:phenyl di-n-pentylphosphinate; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase