An important factor for successful therapy of
poisoning with
organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal,
oximes are administered for reactivation of inhibited
acetylcholinesterase (AChE). Unfortunately, clinically used
oximes, e.g.
obidoxime and
pralidoxime, are of limited effectiveness in
poisoning with different OP
nerve agents requiring the search for alternative
oximes, e.g.
HI 6. In view of substantial species differences regarding reactivation properties of
oximes, the effect of
HI 6 was investigated with
sarin,
tabun and
soman exposed human intercostal muscle. Muscle force production by indirect field stimulation and the activity of the human muscle AChE was assessed. 30 μM
HI 6 resulted in an almost complete recovery of
sarin blocked muscle force and in an increase of completely inhibited muscle AChE activity to approx. 30% of control. In
soman or
tabun exposed human intercostal muscle
HI 6 (50 and 100 μM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition,
HI 6 up to 1000 μM had no effect on
soman blocked muscle force indicating that this
oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial
therapeutic effect on
nerve agent blocked neuromuscular transmission.