The ability of two novel bispyridinium
oximes K727 and K733 and currently available
oximes (HI-6, obidoxime) to reactivate
sarin-inhibited
acetylcholinesterase and to reduce acute toxicity of
sarin was evaluated. To investigate the reactivating efficacy of the
oximes, the rats were administered intramuscularly with
atropine and
oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of
sarin at a dose of 24 µg/kg (LD50). The activity of
acetylcholinesterase was measured at 60 min after
sarin poisoning. The LD50 value of
sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of
sarin at five different doses. In vivo determined percentage of reactivation of
sarin-inhibited rat blood, diaphragm and brain
acetylcholinesterase showed that the potency of both novel
oximes K727 and K733 to reactivate
sarin-inhibited
acetylcholinesterase roughly corresponds to the reactivating efficacy of
obidoxime. On the other hand, the
oxime HI-6 was found to be the most efficient reactivator of
sarin-inhibited
acetylcholinesterase. While the
oxime HI-6 was able to reduce the acute toxicity of
sarin >3 times, both novel
oximes and
obidoxime decreased the acute toxicity of
sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel
oximes K727 and K733 is significantly lower compared to the
oxime HI-6 and, therefore, they are not suitable for the replacement of the
oxime HI-6 for the antidotal treatment of acute
sarin poisoning.