Acute behavioral toxicity of pyridostigmine or soman in primates.

Abstract

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 micrograms/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.

• Authors: D W Blick, M R Murphy, G C Brown, M G Yochmowitz, J W Fanton, S L Hartgraves
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 126 Issue 2 Pg. 311-8 (Jun 1994) ISSN: 0041-008X [Print] United States
• PMID: 8209384 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Soman
• Cholinesterases
• Pyridostigmine Bromide

Topics

• Animals
• Behavior, Animal (drug effects)
• Cholinesterases (blood)
• Dose-Response Relationship, Drug
• Macaca mulatta
• Male
• Pyridostigmine Bromide (toxicity)
• Soman (toxicity)