Reactivators of organophosphate-inhibited cholinesterase.

Two isomeric cyclopentylcarbonyl and two cycloheptylcarbonyl derivatives of 2-hydroxyiminomethyl-1-[3-(1-pyridinio-2-oxapropyl] pyridinium diiodide and 4-hydroxyiminomethyl-1-[3-(1-pyridinio-2-oxapropyl] pyridinium diiodide were prepared and characterized by spectroscopic methods. The inhibitory power (I) of the investigated oximes was determined using purified bovine erythrocyte AChE and human erythrocyte AChE. Percentage of reactivation after 30 min was estimated after inhibition of human erythrocyte AChE by sarin, VX, tabun, soman, and paraoxon. The in vitro protective indices (p.i. and P) against inhibition by soman have been calculated using bovine erythrocyte AChE for p.i. and human erythrocyte AChE for P. Their I for human erythrocyte AChE varied from 1.4-9.8 (10 mol · dm) and for bovine erythrocyte AChE in the range of 1.1-17 (10 mol · dm). With 2 × 10 mol · dm oximes the percent of reactivation was: 0-17% for paraoxon-inhibited AChE, 9-49% for sarin-inhibited AChE, 16-65% for VX-inhibited AChE, 0-8% for tabun-inhibited AChE, and 0-4% for soman-inhibited AChE. The 2-hydroxyimino derivatives protect human erythrocyte AChE and purified bovine erythrocyte AChE from inhibition by soman. [ABSTRACT FROM AUTHOR]