Evaluation of the efficacy of two carbamates, physostigmine and pyridostigmine, when used in conjunction for protection against organophosphate exposure.
Recent studies have shown that pretreatment with either pyridostigmine (PYR) or physostigmine (PHY) followed by atropine-oxime therapy is very effective in reducing the lethality of nerve agents. The therapeutic efficacy of a PHY and PYR combination pretreatment was evaluated in guinea pigs challenged with two LD50s of soman. Endpoints measured were percentage of acetylcholinesterase inhibition induced by the pretreatment and survival up to 24 hr postchallenge. Response surface methodology was employed to describe the relationship between each endpoint and the pretreatment combination. Although both carbamates contributed to blood acetylcholinesterase inhibition, PHY alone protected as well as the optimal dose of the combination.
Solana
R P
RP
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Gennings
C
C
Carter
W H
WH
Anderson
D
D
Lennox
W J
WJ
Carchman
R A
RA
Harris
L W
LW
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D002800:Cholinesterase Inhibitors; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D008954:Models, Biological; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010830:Physostigmine / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D012044:Regression Analysis; D012999:Soman / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012999:Soman; D010830:Physostigmine; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide