The protection of primates against soman poisoning by pretreatment with pyridostigmine

Abstract

The effectiveness of pyridostigmine pretreatment against soman poisoning has been determined in rhesus monkeys and marmosets receiving atropine therapy. Pretreatment with the maximum sign‐free dose (200 μg kg−1, i.v.) raised the subcutaneous LD50 of soman by a factor of 28 in rhesus monkeys and 15 in marmosets. Theprotection afforded by a quarter of the sign‐free dose of pyridostigmine was not significantly less. These levels of protection are higher than any reported in non‐primate species.

Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX

“…Current medical countermeasures against OP nerve agent poisoning include a combination of pretreatment with a carbamate, pyridostigmine bromide, to protect a fraction of AChE from irreversible inhibition by OPs, followed by post-exposure treatment with anticholinergic drugs such as atropine sulfate to counteract the effects of excess acetylcholine, and oximes such as 2-PAM chloride, to reactivate OP-inhibited AChE. These antidotal regimens are effective in preventing lethality of animals from OP poisoning, but they do not prevent post-exposure incapacitation, convulsions, performance deficits or in many cases, permanent brain damage [2][3][4].…”

Proceedings of the 2001 ECBC Scientific Conference on Chemical and Biological Defense Research, 6-8 March 2001, Marriott's Hunt Valley Inn, Hunt Valley, MD

“…Such an association between mortality and status epilepticus is well recognized in the clinical medical literature (Towne et al 1994; Krumholz et al 1995). The fact that control of nerve agent seizures is so strongly linked to protection from the lethal effects of nerve agents may explain the requirement for such high doses of atropine that have been routinely used in studies of the protective effects of carbamate pretreatment (Dirnhuber et al 1979;Maxwell et al 1988) or oxime therapies (Melchers et al 1994;Worek et al 1994; Koplovitz et al 1995). These findings lend perspective to the older reports that inclusion of a benzodiazepine to standard atropine and oxime therapy would increase the protective ratios against OP nerve agent exposure (Johnson and Wilcox 1975;Boskovic 1981).…”

Prophylaxis Against Nerve Agent Intoxications

“…Also, the evidence of pyridostigmine pretreatment strongly enhancing post-exposure antidote therapy for soman poisoning 31,32 was found. This approach shows the strongest benefit of pyridostigmine pretreatment in comparison with atropine and oxime therapy alone in animals challenged with nerve agents [33][34][35][36][37] .…”