Reactivators of organophosphate-inhibited cholinesterase. Phenylhydroxymethyl and cyclohexylhydroxymethyl substituted bis-pyridinium monooximes.

Eleven isomeric phenylhydroxymethyl and cyclohexylhydroxymethyl derivatives of 1-(2-hydroxyiminomethyl-1-pyridinio)-3-(1-pyridinio)-2-oxapropane diiodide and 1-(4-hydroxyiminomethyl-1-pyridinio)-3-(1-pyridinio)-2-oxapropane diiodide were prepared and characterized by spectroscopic methods and pKa values. The inhibitory power (I50) of the investigated oximes was determined on 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, and paraoxon. The in vitro protective index against inhibition by soman has been calculated using bovine erythrocyte AChE. Their I50 for human erythrocyte AChE varied in the range of 9-61(10(-4) mol. dm-3) and for purified bovine erythrocyte AChE in the range of 11-57 (10(-5) mol . dm-3). With 2 X 10(-5) mol . dm-3 of oximes the percent of reactivation was: 0-63% for paraoxon inhibited AChE, 12-73% for sarin inhibited AChE and 11-80% for VX inhibited AChE. With the exception of 1-(2-hydroxyiminomethyl-1-pyridinio)-3-(4-phenylhydroxymethyl-1-pyridinio) -2-oxapropane diiodide (6) the derivatives of 4-hydroxyiminomethylpyridine are by far better reactivators. None of the compounds could protect purified bovine erythrocyte AChE from inhibition by soman.