RT Journal Article
SR Electronic
T1 Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 633
OP 638
VO 259
IS 2
A1 C A Broomfield
A1 D M Maxwell
A1 R P Solana
A1 C A Castro
A1 A V Finger
A1 D E Lenz
YR 1991
UL http://jpet.aspetjournals.org/content/259/2/633.abstract
AB 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.