Use of cholinesterases as pretreatment drugs for the protection of rhesus monkeys against soman toxicity.
Purified fetal bovine serum acetylcholinesterase (FBS AChE) and horse serum butyrylcholinesterase (BChE) were successfully used as single pretreatment drugs for the prevention of pinacolyl methylphosphonofluoridate (soman) toxicity in nonhuman primates. Eight rhesus monkeys, trained to perform Primate Equilibrium Platform (PEP) tasks, were pretreated with FBS AChE or BChE and challenged with a cumulative level of five median lethal doses (LD50) of soman. All ChE-pretreated monkeys survived the soman challenge and showed no symptoms of soman toxicity. A quantitative linear relation was observed between the soman dose and the neutralization of blood ChE. None of the four AChE-pretreated animals showed PEP task decrements, even though administration of soman irreversibly inhibited nearly all of the exogenously administered AChE. In two of four BChE-pretreated animals, a small transient PEP performance decrement occurred when the cumulative soman dose exceeded 4 LD50. Performance decrements observed under BChE protection were modest by the usual standards of organophosphorus compound toxicity. No residual or delayed performance decrements or other untoward effects were observed during 6 weeks of post-exposure testing with either ChE.
Wolfe
A D
AD
Division of Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Blick
D W
DW
Murphy
M R
MR
Miller
S A
SA
Gentry
M K
MK
Hartgraves
S L
SL
Doctor
B P
BP
D000110:Acetylcholinesterase / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002091:Butyrylcholinesterase / Q000494:pharmacology*; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D005500:Follow-Up Studies; D006736:Horses; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D011597:Psychomotor Performance / Q000187:drug effects; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D012999:Soman; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase