A newly developed oxime K203 is the most effective reactivator of tabun-inhibited acetylcholinesterase.

Abstract

BACKGROUND:

Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes.

METHODS:

To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6).

RESULTS:

Reactivation studies showed that K203 was the most effective reactivator with a second order kinetic constant (kr) of 2142 min- 1. M- 1, which was 51 times higher than that obtained for obidoxime (kr = 42 min- 1. M- 1). Both pralidoxime and asoxime (HI-6) failed to significantly reactivate tabun-inhibited human AChE.

DISCUSSION:

According to these results and previous studies, using K203, it appears that oxime K203 is the most effective reactivator of tabun-inhibited cholinesterase in several species including humans and should be considered as a possible medical countermeasure to tabun exposure.

• Authors: Kamil Kuca, Kamil Musilek, Daniel Jun, Jana Zdarova-Karasova, Eugenie Nepovimova, Ondrej Soukup, Martina Hrabinova, John Mikler, Tanos C C Franca, Elaine F F Da Cunha, Alexandre A De Castro, Martin Valis, Teodorico C Ramalho
• Journal: BMC pharmacology & toxicology (BMC Pharmacol Toxicol) Vol. 19 Issue 1 Pg. 8 (02 21 2018) ISSN: 2050-6511 [Electronic] England
• PMID: 29467029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene
• Antidotes
• Cholinesterase Inhibitors
• Cholinesterase Reactivators
• Organophosphates
• Oximes
• Pyridinium Compounds
• Acetylcholinesterase
• tabun

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Antidotes (metabolism)
• Brain (enzymology)
• Cholinesterase Inhibitors (metabolism)
• Cholinesterase Reactivators (metabolism)
• Humans
• Molecular Docking Simulation
• Organophosphates (metabolism)
• Oximes (metabolism)
• Pyridinium Compounds (metabolism)
• Rats