Toxicity of Anticholinesterases: Interactions of Pyridostigmine and Physostigmine with Soman

摘要

This investigation was conducted to assess the potential of carbamate pretreatment to exacerbate the ill effects of low dose of soman. Ambulatory Activity in a photocell cage (AA) and performance time on an accelerating rotarod (ARR) were used to test for interactions between pyridostigmine or physostigmine and soman. ED50s (i.e., dosages sufficient to reduce ARR time and AA to 50% of control level) of each carbamate (IM) and soman (SC) were determined. The ED50 values (mg/kg) in the ARR test were 3.2, 0.21, and 0.72 for pyridostigmine, physostigmine and soman, respectively, while in the AA test corresponding values were 1.8, 0.072, and 0.060. The matrix of 16 combinations of 0, 1, 2/3, and 1/3 ED50 each of carbamate and soman was studied in each test system, as well as the effect of behavioral deficit free (BDF)Dosages of each carbamate on the ED50s of soman. In both the AA and ARR tests the matrix of combinations of pyridostigmine and soman indicated an additive effect. In contrast, physostigmine produced one instance of potentitation in each test system and antagonism in two combinations in the AA procedure. A BDF dosage of each carbamate (0.056 mg/kg of pyridostimgine and 0.26 mg/kg of physostigmine) gave no evidence of adding to the deficit in AA induced by soman. In the ARR test, the ED50 of soman was lower by 11% with pyridostimgine pretreatment and by 14% with physostigmine; the latter just reached statistical significance(p < 0.05)