The standard treatment of
poisoning by
organophosphorus compounds (OP) includes the reversible
muscarine receptor antagonist
atropine and
oximes for the reactivation of OP-inhibited
acetylcholinesterase (AChE). There is an ongoing discussion on the benefit of
oxime therapy in OP
pesticide poisoning, and experimental data indicate a limited efficacy of
oximes against various
nerve agents.
Oxime effectiveness can be quantified in vitro by determination of the reactivity (k(r)) and affinity constants (1/K(D)). These constants can be used to calculate reactivation velocities and
oxime concentrations necessary for the reactivation of a desired fraction of inhibited AChE. Model calculations indicate that a k(r) > 0.1 min(-1) and K(D) < 100 µM are minimal requirements for
oxime effectiveness when reactivation is performed in the absence of free OP. In addition, the findings demonstrate that selective increase of either reactivity or affinity of an
oxime would be insufficient. Hereby, it has to be taken into account that an increase of affinity to OP-inhibited AChE is generally accompanied by an increased affinity to native AChE and subsequent reduction in
oxime tolerance. Hence, future developments of more effective
oximes should consider kinetic demands by attempting to achieve a certain level of reactivity and affinity, preferentially towards OP-inhibited AChE.