The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of tabun poisoning in rats and mice

Abstract

The influence of the combination of oximes on the reactivating and therapeutic efficacy of antidotal treament of acute tabun poisoning was evaluated. The ability of two combinations of oximes (HI-6 + obidoxime and HI-6 + K203) to reactivate tabun-inhibited acetylcholinesterase and reduce acute toxicity of tabun was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, obidoxime, K203) using in vivo methods. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is higher than the reactivating efficacy of the most effective individual oxime in blood and diaphragm and comparable with the reactivating effects of the most effective individual oxime in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in tabun-poisoned mice than the antidotal treatment involving individual oxime. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the newly developed oxime K203 is slightly more effective than commonly used obidoxime and both of them are markedly more effective than the oxime HI-6. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings beneficial effects for the potency of antidotal treatment to reactivate tabun-inhibited acetylcholinesterase in rats and to reduce acute toxicity of tabun in mice.

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

“…Such in-vivo recovery of AChE activity depends on the type of oxime in use, concentration levels of 10 -4 -10 -5 M being considered suitable for reactivation. However, lower concentration levels have been reported to produce significant AChE reactivation (Kassa et al, 2008a(Kassa et al, , 2008b(Kassa et al, , 2010.…”

“…The central reactivation effects and the recovery of AChE activity in different brain locations was demonstrated (Bajgar et al, 1975;Kassa and Kunesova, 2006;Kassa et al, 2008b;Kassa et al, 2010) following administration of the reactivators to animals intoxicated with nerve agents.…”

Efficient Charge Separation in TiO2 Films Sensitized with Ruthenium(II)–Polypyridyl Complexes: Hole Stabilization by Ligand‐Localized Charge‐Transfer States

“…Such in‐vivo recovery of AChE activity depends on the type of oxime in use, concentration levels of 10 −4 –10 −5 m being considered suitable for reactivation. However, lower concentration levels have been reported to produce significant AChE reactivation (Kassa et al ., 2008a, 2008b, 2010).…”

“…The inhibition process and the consequent reactivation of AChE in brain represents selective processes, depending on the OP nature (Bajgar et al ., 1975, 2008; Bajgar, 2004). The central reactivation effects and the recovery of AChE activity in different brain locations was demonstrated (Bajgar et al ., 1975; Kassa and Kunesova, 2006; Kassa et al., 2008b; Kassa et al ., 2010) following administration of the reactivators to animals intoxicated with nerve agents.…”

Blood–Brain Barrier Damage and Dysfunction by Chemical Toxicity

“…In OP nerve agent poisoning, a combination of AChE reactivating oximes provides better therapeutic efficacy compared with an individual oxime (Kassa et al, 2010(Kassa et al, , 2011a. Also, oximes (pralidoxime, trimedoxime, obidoxime, HI-6, HLo-7) provide greater neuroprotection against OP nerve agents when given in combination with an antimuscarinic drug (e.g., atropine sulfate) and an anticonvulsant drug (e.g., diazepam).…”