title: Cresylbenzodioxaphosphorin oxide pretreatment alters soman-induced toxicity and inhibition of tissue cholinesterase activity of the rat.
abstract: The toxicity of soman was investigated in the rat with and without pretreatment with cresylbenzodioxaphosphorin oxide (CBDP). Without pretreatment, the 24-h LD50 for soman was 118.2 micrograms/kg s.c., and soman inhibited carboxylesterase (CaE) activity in plasma (ED50 of 55 micrograms/kg) and cholinesterase (ChE) activity in brain regions (ED50 values of 65-105 micrograms/kg) in a dose-related manner. With pretreatment, the 24-h LD50 for soman was reduced by approximately 6-fold and 8-fold (by 1.0 mg/kg and 16.0 mg/kg of CBDP, respectively), and the ED50 values for soman-induced inhibition of ChE activity in brain regions were reduced by approximately 10-fold (by 1.0 mg/kg of CBDP). The dose-dependent severity of soman intoxication varied widely in rats treated with soman alone but not in CBDP-pretreated rats, and the ED50 for the occurrence of signs of soman intoxication was reduced approximately 7-fold following CBDP (1.0 mg/kg) pretreatment. These data support the hypothesis that CBDP pretreatment effectively blocks tissue CaE sites which serve to detoxify soman, thus potentiating both the soman-induced inhibition of ChE in the CNS and the lethality of soman.
authors.affiliation: Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
authors.forename: V R
authors.initials: VR
authors.lastname: Jimmerson
authors.forename: T M
authors.initials: TM
authors.lastname: Shih
authors.forename: D M
authors.initials: DM
authors.lastname: Maxwell
authors.forename: R B
authors.initials: RB
authors.lastname: Mailman
mesh_terms: D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D002490:Central Nervous System / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors; D004357:Drug Synergism; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D012999:Soman; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase