Acute Behavioral Toxicity of Pyridostigmine or Soman in Primates

• Published in: Toxicology and applied pharmacology Vol. 126; no. 2; pp. 311 - 318
• Main Authors: Blick, D.W., Murphy, M.R., Brown, G.C., Yochmowitz, M.G., Fanton, J.W., Hartgraves, S.L.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.06.1994; Elsevier
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Cholinesterases - blood; Dose-Response Relationship, Drug; Macaca mulatta; Male; Medical sciences; Pyridostigmine Bromide - toxicity; Soman - toxicity; Toxicology; Various organic compounds; Nervous system diseases; Toxicity; Acute; Monkey; Tracking task; Organic carbamate; Vertebrata; Mammalia; Animal; Primates; Organophosphorus compounds; Anticholinesterase agent; Behavior; Soman; Carbamate; Comparative study
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1994.1121

Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 μg/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxicity. We also found that soman, an irreversible inhibitor of acetylcholinesterase (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 behavioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect performance. As a prophylactic treatment for OP agent poisoning, pyridostigmine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose.