Toxicity of anticholinesterases: interactions of pyridostigmine and physostigmine with soman.
This investigation was conducted to assess the potential of carbamate pretreatment to exacerbate the ill effects of low doses 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 0.072 for pyridostigmine, physostigmine and soman, respectively, while in the AA test the 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 potentiation in each test system and anatagonism in two combinations in the AA procedure. A BDF dosage of each carbamate (0.056 mg/kg of pyridostigmine and 0.026 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 pyridostigmine pretreatment and by 14% with physostigmine; the latter just reached statistical significance (p less than 0.05). Although additivity was most often found at higher dosages of pyridostigmine and physostigmine, at the BDF dosages little or no adverse interaction was found between Pyridostigmine or Physostigmine and low levels of soman.
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D004347:Drug Interactions; D007928:Lethal Dose 50; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010830:Physostigmine / Q000633:toxicity*; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*
D009943:Organophosphorus Compounds; D012999:Soman; D010830:Physostigmine; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide