title: Primate performance decrements following acute soman exposure: failure of chemical countermeasures.
abstract: Three experiments are reported: 1) a feasibility study on using laboratory primates repeatedly in behavioral toxicity studies of organophosphate (OP) agents or of chemical countermeasures against OPs; 2) a study of the efficacy of pyridostigmine pretreatment and 2-PAM therapy; and 3) a study to determine the effects of these treatments on soman-induced cholinesterase (ChE) inhibition and its recovery. In rhesus monkeys, three repeated acute low-dose (2.1 to 2.8 micrograms/kg) soman exposures, separated by intervals > 5 weeks, did not change baseline compensatory tracking performance or the soman ED50. Atropine therapy (97 micrograms/kg) alone had no effect on soman ED50. Addition of pyridostigmine pretreatment (150 micrograms/kg) and 2-PAM therapy (17 mg/kg) to atropine therapy increased the soman ED50 for a performance decrement from 2.27 micrograms/kg to 2.58 micrograms/kg, an insignificant protective effect. At the soman ED50 for behavioral decrements, pyridostigmine pretreatment increased the inhibition of serum ChE observed immediately after soman exposure, but reduced the extent of permanent inhibition. The 2-PAM therapy reduced serum ChE inhibition from about 80% to less than 70%. These effects on the time course of ChE inhibition following soman exposure appear to combine additively. These chemical countermeasures do not prevent soman-induced performance decrements, even though they are effective in protecting lives after much higher doses. The soman doses used produce only small, transient performance decrements; animals so exposed can, thus, be used repeatedly in such studies.
authors.affiliation: Systems Research Laboratories Division of Arvin/Calspan, Brooks AFB, Texas 78235-5000.
authors.forename: D W
authors.initials: DW
authors.lastname: Blick
authors.forename: M R
authors.initials: MR
authors.lastname: Murphy
authors.forename: G C
authors.initials: GC
authors.lastname: Brown
authors.forename: S L
authors.initials: SL
authors.lastname: Hartgraves
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D012999:Soman / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D002801:Cholinesterase Reactivators; D011220:Pralidoxime Compounds; D001285:Atropine; D012999:Soman; D002802:Cholinesterases; D011729:Pyridostigmine Bromide; C028797:pralidoxime