Muscle force and acetylcholinesterase activity in mouse hemidiaphragms exposed to paraoxon and treated by oximes in vitro

The therapy of organophosphorus compound (OP) poisoning is still a challenge to clinical toxicologists To alleviate peripheral respiratory failure oximes, e g obidoxime and pralidoxime, are used to reactivate inhibited acetylcholinesterase (AChE) with the intention to restore the disturbed neuromuscular function. In severe human OP poisoning the persistence of poison may counteract effective reactivation by oximes. Therefore, the study was designed to investigate the effect of the clinically used oximes obidoxime, pralidoxime and the experimental compounds HI 6 and HLo 7 in the presence of different paraoxon concentrations The mouse phrenic nerve-diaphragm preparation was used as a functional model. After washout of paraoxon remarkably low concentrations of obidoxime or HLo 7 were sufficient for restoration of paraoxon-impaired muscle force In the presence of paraoxon, obidoxime was the most effective oxime and therapeutically used concentrations (10-20 mu M) were able to restore muscle function even in the presence of 1 mu M paraoxon HLo 7 was less effective, but superior to HI 6 and pralidoxime Generally, a reactivation of AChE to about 30-40% of normal was sufficient for restoration of muscle force Thus, the data presented strongly support the administration of appropriately dosed oximes, preferably obidoxime, in paraoxon-poisoned patients to restore paraoxon-impaired muscle force (C) 2010 Elsevier Ireland Ltd All rights reserved.