The use of organophosphorus pesticides results in toxicity risk to non-target organisms.
Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via
acetylcholinesterase (AChE) inhibition. Consequently,
acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of
cholinergic receptors. Acute
cholinergic crisis immediately follows exposure to
organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral
muscarinic and
nicotinic receptors. The current view of the treatment of
organophosphate poisoning includes three strategies, i.e. the use of an
anticholinergic drug (e.g.,
atropine),
cholinesterase-reactivating agents (e.g.,
oximes) and
anticonvulsant drugs (e.g.,
benzodiazepines).
Oximes, as a part of antidotal
therapy, ensure the recovery of phosphylated
enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different
oximes are not equally effective against
poisonings caused by structurally different
organophosphorus compounds. Therefore, antidotal characteristics of conventionally used
oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal
oxime.
Pralidoxime (PAM-2),
trimedoxime (TMB-4),
obidoxime (LüH-6),
HI-6 and HLö-7 have all been demonstrated to be very effective in experimental
poisonings with
sarin and
VX.
TMB-4 and LüH-6 may reactivate
tabun-inhibited AChE, whereas
HI-6 possesses the ability to reactivate the
soman-inhibited
enzyme. An
oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the
oximes LüH-6 and
TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of controlled clinical trials on the use of
TMB-4 in human
organophosphate pesticide poisoning, LüH-6 may be a better option.