Efficacy of Physostigmine Plus Cholinolytic versus Physostigmine Plus Pyridostigmine Plus Cholinolytic against Soman-Induced Lethality and Physical Incapacitation

摘要

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 (PHY/PYR) combination pretreatment was evaluated in guinea pigs challenged with 2 LD50's of soman. Four endpoints were measured: percent acetylcholinesterase inhibition induced by the pretreatment, survival up to 24 hours post-challenge, maximum post-soman behavioral decrement on rotarod, and time to recovery post-soman. Regression techniques were 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. There is no indication that the combination minimizes behavioral deficits or reduces time to recovery over a pretreatment of PHY alone. In fact a subtle increase in pretreatment toxicity is evident at high doses of the combination. (AW)