ACUTE BEHAVIORAL TOXICITY OF PYRIDOSTIGMINE OR SOMAN IN PRIMATES

Effects of a peripherally active carbamate (pyridostigmine bromide) an d a centrally active organophosphate (OP) nerve agent (soman) on perfo rmance by rhesus monkeys of a compensatory tracking (primate equilibri um platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the u p-and-down (titration) method to determine the ED50 for soman (2.50 mu g/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxici ty. We also found that soman, an irreversible inhibitor of acetylcholi nesterase (AChE), is more than 100 times more behaviorally disruptive than the reversible peripheral inhibitor pyridostigmine, as indicated by the difference in ED50 doses expressed in molar terms. Soman's beha vioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect perfor mance. As a prophylactic treatment for OP agent poisoning, pyridostigm ine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose. (C) 1994 Academic Press, Inc.