title: A comparison of the efficacy of acetylcholinesterase reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods.
abstract: The purpose of this study was to compare the therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-(2-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium )-2-butene dibromide), with presently used oximes (pralidoxime, obidoxime, methoxime) and H-oximes (HI-6, HLö-7) by in vitro and in vivo methods. In vitro, methoxime seems to be the most efficacious reactivator of GF agent-inhibited acetylcholinesterase because the phosphorylation of acetylcholinesterase by GF agent markedly increases its affinity for the enzyme. The oxime BI-6 is more efficacious than other presently used oximes (pralidoxime, obidoxime) but its reactivating efficacy does not reach the efficacy of H-oximes tested. On the other hand, obidoxime and pralidoxime appear to be very poor reactivators of GF agent-inhibited acetylcholinesterase because the phosphonylation of acetylcholinesterase by GF agent markedly decreases their affinity to the enzyme. In vivo, H oximes (HI-6, HLö-7) are the most efficacious antidotes for the treatment of acute poisoning with GF agent in rats while the presently used oximes such as pralidoxime and obidoxime are practically ineffective. BI-6 and methoxime are more efficacious than pralidoxime and obidoxime, nevertheless their therapeutic efficacy does not reach the efficacy of H oximes. Our results show that the ability of oximes to reactivate GF agent-inhibited acetylcholinesterase in vitro usually corresponds to their therapeutic effects against GF agent in vivo.
authors.affiliation: Purkynĕ Military Medical Academy, Hradec Králové Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kassa
authors.forename: J
authors.initials: J
authors.lastname: Cabal
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004793:Enzyme Reactivators / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate