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 HLö 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 HLö 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 (10-20microM) were able to restore muscle function even in the presence of 1microM
paraoxon. HLö 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.