title: Evaluation of phosphinates as potential pretreatments for nerve agents.
abstract: To assess the utility of phosphinates as pretreatments against nerve agents, experiments were conducted to determine whether oximes can reactivate phosphinate-inhibited guinea pig acetylcholinesterase (AChE) and whether the toxicity of phosphinates is reduced by treatment with atropine and/or oxime. Three phosphinates, 4-nitrophenyl methyl(phenyl) phosphinate (MPP), 4-nitrophenyl chloromethyl(phenyl) phosphinate (CMPP), and 4-nitrophenyl 2-methoxyphenyl(methyl) phosphinate (MPMP), were used in these experiments. In the first group of experiments, 2-PAM or HI-6 was administered, im, 2 min after peak inhibition of whole blood AChE activity by the phosphinates. Both oximes significantly reactivated MPP- or CMPP-inhibited AChE; however, HI-6 was the better reactivator in both cases. Oximes were ineffective against MPMP. Efficacy studies revealed that neither HI-6 nor 2-PAM potentiated the toxic effects of MPP or CMPP and that atropine/oxime therapy provided greater protection (up to 100 LD50s) against either phosphinate than any single therapy. The reactivation and efficacy data, especially for CMPP, support the concept that oxime sensitive phosphinates may be useful as pretreatments against nerve agent intoxication.
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
authors.forename: D R
authors.initials: DR
authors.lastname: Anderson
authors.forename: L W
authors.initials: LW
authors.lastname: Harris
authors.forename: C N
authors.initials: CN
authors.lastname: Lieske
authors.forename: W J
authors.initials: WJ
authors.lastname: Lennox
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D002801:Cholinesterase Reactivators / Q000008:administration & dosage*; D005069:Evaluation Studies as Topic; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D007928:Lethal Dose 50; D008297:Male; D009578:Nitrobenzenes / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes; D011220:Pralidoxime Compounds / Q000008:administration & dosage*; D011726:Pyridinium Compounds / Q000008:administration & dosage*
chemical_list: D002801:Cholinesterase Reactivators; D009578:Nitrobenzenes; D009943:Organophosphorus Compounds; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; C049498:O-4-(nitrophenyl)methylphenyl phosphinate; D001285:Atropine; C069334:4-nitrophenyl chloromethyl(phenyl)phosphinate; D000110:Acetylcholinesterase; C022870:asoxime chloride; C028797:pralidoxime