Cholinesterase Activity in Guinea Pigs Following Intravenous Exposure to the Optically Pure Enantiomers of VX
Abstract
The center phosphorus atom of VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) rotates linearly polarized light both clockwise (P(+)-isomer) and anticlockwise (P()-isomer) so that its synthesis results in equal amounts of two enantiomers with the same chemical and physical properties. The toxicological properties of the two enantiomers, however, are anticipated to be different because they exert their effects in a chiral, biologic environment. We recently estimated median lethal doses (24 h LD50) for intravenous exposure to the optically pure enantiomers of VX in adult, male guinea pigs; the P(+)-isomer of VX was 60 less toxic than the P()-isomer. Serial blood samples were collected from a subset of these guinea pigs to characterize the toxicodynamic profile of each enantiomer. Acetylcholinesterase (AChE) activity was inhibited more slowly with the P(+)-isomer of VX than with the P()-isomer. In addition, the P(+)-isomer of VX inhibited nearly 95% of the butyrylcholinesterase (BuChE) activity compared to only 40% with the P()-isomer. The stereoselectivity differences between AChE and BuChE inhibition may explain why the P(+)-isomer of VX was less toxic than the P()-isomer in the guinea pig model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1107833
Entities
People
- Bernardita I. Gaviola
- David C. Burnett
- Linnzi K. Wright
- Susan L Byers
Organizations
- United States Army Combat Capabilities Development Command