OXIME-INDUCED REACTIVATION OF ACETYLCHOLINESTERASE INHIBITED BY PHOSPHORAMIDATES

The reaction of human erythrocyte acetylcholinesterase (AChE) with a s et of structurally related phosphoramidates was studied in order to in vestigate the properties of phosphorylated enzyme and the effects of 4 oximes PAM-2, TMB-4, HI-6 and BDB-106 on the reactivation of inhibite d AChE. Second-order rate constant of the phosphorylation reaction of the compounds towards the active site of AChE ranged between 5.0 x 10( 2) and 4.9 x 10(6) M(-1)min(-1) and their inhibitory power (I-50) was from 7.3 x 10(-5) to 5.7 x 10(-9) M for 20 min incubation at 37 degree s C. The oximes used were weak reactivators of inhibited AChE except f or (C4H9O)(NH2)P(O)DCP (DCP, -O-2,5-dichlorphenyl group) and (C6H13O)( NH2)P(O)SCH3 where we have obtained good reactivation. Imidazole oxime BDB-106 proved to be a potent reactivator of tabun-inhibited AChE.