Reduction by pyridostigmine pretreatment of the efficacy of atropine and 2-PAM treatment of sarin and VX poisoning in rodents.
This study concerned the effect of pyridostigmine pretreatment on (a) the antidotal efficacy of atropine and 2-PAM in sarin, tabun, and VX poisoning in mice and guinea pigs and on (b) the oxime-induced reactivation of VX-inhibited whole blood acetylcholinesterase (AChE) of guinea pigs. One hour prior to organophosphate (OP) challenge with sarin, tabun, or VX, animals were given oral doses of pyridostigmine to induce approximately 30 and 60% inhibition of whole blood AChE; controls received vehicle. Mice were challenged im and guinea pigs sc with the OP compounds. Treatment with atropine (11.2 mg/kg to mice; 32 mg/kg to guinea pigs) plus 2-PAM (25 mg/kg) was given im at 10 sec postchallenge in mice and 1 min postchallenge in guinea pigs. In the reactivation experiments, pyridostigmine or saline was given im to guinea pigs 30 min prior to VX (8.24 micrograms/kg, sc), atropine (16 mg/kg) was given im at 1 min, and 2-PAM (25 mg/kg) at 16 min postchallenge. Pyridostigmine significantly enhanced the efficacy of atropine and 2-PAM against tabun in both species. In contrast, pyridostigmine reduced or did not increase the efficacy of atropine and 2-PAM against sarin or VX in both species. Recovery of VX-inhibited AChE by 2-PAM was decreased significantly in pyridostigmine pretreated animals. The results suggest that pyridostigmine pretreatment may adversely effect the efficacy of atropine and 2-PAM as antidotes for VX and sarin intoxication.
Koplovitz
I
I
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Harris
L W
LW
Anderson
D R
DR
Lennox
W J
WJ
Stewart
J R
JR
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D062025:Organophosphate Poisoning; D010755:Organophosphates / Q000037:antagonists & inhibitors; D009946:Organothiophosphorus Compounds / Q000037:antagonists & inhibitors / Q000506:poisoning*; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D012524:Sarin / Q000037:antagonists & inhibitors / Q000506:poisoning*
D000110:Acetylcholinesterase; D001285:Atropine; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D009946:Organothiophosphorus Compounds; D011220:Pralidoxime Compounds; D011729:Pyridostigmine Bromide; D012524:Sarin; C009680:VX-agent; C009374:tabun