Post‐exposure protection against nerve agent‐induced lethality without carbamate pretreatment in guinea pigs

Abstract

Managing organophosphorus nerve agent poisoning involves pyridostigmine (PYR) pretreatment followed by post‐exposure oxime/anticholinergic therapy. For military/civilian populations not enrolled in the PYR pretreatment program, however, the post‐exposure therapy offers little, if any, protection. To eliminate the need for pretreatment, we have developed, and efficacy evaluated, a post‐exposure therapy mix consisting of scopolamine (0.5 mg/kg, im), methyl‐atropine (2 mg/kg, im), physostigmine (0.015 mg/kg, im), MMB4 (a bispyridinium oxime; 26.1 mg/kg, im) and phenobarbital (25 mg/kg, ip) against a lethal dose (2×LD50) of either soman (GD), sarin (GB), cyclo‐sarin (GF) or VX in unanesthetized guinea pigs instrumented for concurrent recordings of CNS and cardiorespiratory activities. Results showed that none of the animals tested exhibited seizures, convulsions or signs of anomalous cardiorespiratory activities. Only mild acute cholinergic effects (salivation, dystonia) and phenobarbital's sedative effects were seen during the first 20 min post‐agent. Animals were typically asymptomatic within 20–30 min. All animals survived 24 hrs post nerve agent exposure. Our findings indicate that the therapy mix used in this study was effective not only in antagonizing nerve agent‐induced lethality, but also in protecting the functional integrity of the CNS and cardiorespiratory system.