Protection of rhesus monkeys against soman and prevention of performance decrement by pretreatment with acetylcholinesterase.
The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman.
Maxwell
D M
DM
Pharmacology Division, United States Army Medical Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Castro
C A
CA
De La Hoz
D M
DM
Gentry
M K
MK
Gold
M B
MB
Solana
R P
RP
Wolfe
A D
AD
Doctor
B P
BP
D000110:Acetylcholinesterase / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D011041:Poisoning / Q000517:prevention & control; D011292:Premedication; D012999:Soman / Q000037:antagonists & inhibitors* / Q000506:poisoning
D012999:Soman; D000110:Acetylcholinesterase