Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates.
Butyrylcholinesterase (BuChE) was examined as an in vivo exogenous scavenger for highly toxic organophosphorus (OP) poisons. Protection studies with equine BuChE were carried out in rhesus monkeys trained to perform a Serial Probe Recognition task. The pharmacokinetics of equine BuChE administered i.v. in rhesus monkeys revealed an elimination T1/2 of approximately 620 hr. Animals given 503 nmol of BuChE i.v. and then challenged with 220 to 260 nmol of soman (two LD50; a lethal dose in untreated animals) all survived with no clinical signs of OP poisoning. Serial Probe Recognition performance was depressed after enzyme administration and at 1 hr postsoman. However, all monkeys performed the task at base-line levels at 8 hr after soman and throughout the remainder of the experimental period. Two different monkeys each were given two doses of sarin, 183 nmol/dose (one LD50) after 460 nmol of BuChE. No signs were observed. A third group of monkeys given 253 or 340 nmol (three and four LD50, respectively) of soman after 460 nmol of BuChE required 1 mg/kg of atropine i.v. 10 min postsoman, but recovered completely within 24 hr. Our results indicate that BuChE has the required properties to function as a biological scavenger to protect against the pharmacological and behavioral toxicity of OP poisons.
Broomfield
C A
CA
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
Maxwell
D M
DM
Solana
R P
RP
Castro
C A
CA
Finger
A V
AV
Lenz
D E
DE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002091:Butyrylcholinesterase / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007858:Learning / Q000187:drug effects; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D062025:Organophosphate Poisoning; D011041:Poisoning / Q000517:prevention & control; D012524:Sarin / Q000633:toxicity; D012999:Soman / Q000633:toxicity
D012999:Soman; D012524:Sarin; D002091:Butyrylcholinesterase