Comparison of antidote protection against soman by pyridostigmine, HI-6 and acetylcholinesterase.
Carbamate, oxime and enzyme scavenger approaches to protection against the highly toxic organophosphorus compound, soman, were compared by using the most prominent example of each type of antidote. Pyridostigmine in combination with atropine, HI-6 [1-(2-(hydroxyimino)methyl))pyridinium-2-(4-(aminocarbonyl)p yridinium) dimethylether] in combination with atropine and fetal bovine serum acetylcholinesterase (FBS-AChE) without atropine were used as examples of oxime, carbamate and enzyme scavenger antidotes, respectively. Each antidotal regimen produced approximately equal maximal protection against the lethal effects of 952 to 1169 nmol/kg (LD50, 8-10) of soman in mice whose carboxylesterase had been inhibited with 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide. FBS-AChE was much better than either pyridostigmine-atropine or HI-6-atropine in reducing postexposure incapacitation from soman as measured by lacrimation, motor dysfunction, activity level and the inverted screen test. A lower dose of pyridostigmine (566 nmol/kg) or FBS-AChE (1150 nmol/kg) was required to protect against 968 nmol/kg (LD50, 8) of soman than was required for HI-6 (200,000 nmol/kg). Inasmuch as the in vivo biological half-life of FBS-AChE (1550 min) was much greater than the biological half-lives of pyridostigmine (48 min) or HI-6 (11 min), the ability of FBS-AChE to produce better protection against the postexposure incapacitation from soman suggests that it should be considered as an alternative to either pyridostigmine-atropine or HI-6-atropine antidotal regimens.
Maxwell
D M
DM
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
Brecht
K M
KM
Doctor
B P
BP
Wolfe
A D
AD
D000110:Acetylcholinesterase / Q000494:pharmacology*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010091:Oximes; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D012999:Soman / Q000037:antagonists & inhibitors* / Q000506:poisoning
D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; D000110:Acetylcholinesterase; C022870:asoxime chloride; D011729:Pyridostigmine Bromide