Pyridostigmine Pretreatment Improves Survival and Reduces Incapacitation in Mice Intoxicated with Soman and Treated with Atropine Sulfate and 2-PAM Chloride

摘要

As part of an ongoing in vivo drug screening program the efficacy of pyridostigmine pretreatment in protection against soman-induced lethality and incapacitation was evaluated in three studies using mice. In the first study, significant incidences of twenty-four hour lethality and physical incapacitation were observed in mice given dosages of 0.90 LD50 or greater of soman. In the second study, mice were pretreated with pyridostigmine (PYR) or vehicle, challenged with 2.0 LD50 of soman, and treated with atropine (ATR) and 2-PAM Chloride (2-PAM). Animals pretreated with PYR manifested significant greater survivability and significantly less incapacition than vehicle-pretreated controls. In the third study, mice pretreated with either 0.20 or 0.82 mg/kg PYR were challenged with one of eight challenge levels of soman and treated with ATR and 2-PAM. Animals pretreated with either dosage of PYR demonstrated significantly enhanced protection from lethality and incapacitation over a range of soman challenges from 1.3 to 2.1 LD50 compared to animals treated with ATR and 2-PAM. No difference in protection was observed between the two PYR dosages. The results of these studies indicate that, in the mouse, pretreatment with PYR affords significant advantage when added to conventional ATR and 2-PAM therapy.