A comparison of the reactivating and therapeutic efficacy of newly developed oximes (K347, K628) with commonly used oximes (obidoxime, HI-6) against tabun in rats and mice. 2010

Jiri Kassa, and Jana Zdarova Karasova, and Kamil Kuca, and Kamil Musilek
Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic. kassa@pmfhk.cz

The potency of newly developed reactivators of nerve agent-inhibited acetylcholinesterase (K347, K628) in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, the oxime HI-6), using in vivo methods. Studies that determined the percentage of reactivation of tabun-inhibited blood and tissue acetycholinesterase in poisoned rats showed that the reactivating efficacy of both newly developed oximes is comparable with the oxime HI-6, but it is significantly lower than the reactivating effects of obidoxime. The monopyridinium oxime, K347, was also found to be able to reduce lethal toxic effects in tabun-poisoned mice, while the therapeutic efficacy of another newly developed bispyridinium oxime, K628, was negligible. The therapeutic efficacy of K347 was higher than the potency of the oxime, HI-6, but it was lower than the therapeutic effects of obidoxime. Thus, the reactivating and therapeutic potency of both newly developed oximes (K347, K628) was not more effective then currently available oximes, and therefore, they are not suitable for the replacement of commonly used oximes (especially obidoxime) for the treatment of acute tabun poisoning.

UI MeSH Term Description Entries
D007928 Lethal Dose 50 The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population. LD50,Dose 50, Lethal
D008297 Male Males
D009768 Obidoxime Chloride Cholinesterase reactivator occurring in two interchangeable isomeric forms, syn and anti. Obidoxim,Obidoxime,Toxogonin,Chloride, Obidoxime
D010091 Oximes Compounds that contain the radical R2C Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
D010755 Organophosphates Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P( Organophosphate,Phosphates, Organic,Phosphoric Acid Esters,Organopyrophosphates,Acid Esters, Phosphoric,Esters, Phosphoric Acid,Organic Phosphates
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D002619 Chemical Warfare Agents Chemicals that are used to cause the disturbance, disease, or death of humans during WARFARE. Agents, Chemical Warfare,Warfare Agents, Chemical,Agent, Chemical Warfare,Chemical Warfare Agent,Warfare Agent, Chemical
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D002801 Cholinesterase Reactivators Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates. Insecticides, Organophosphate, Antagonists,Insecticides, Organothiophosphate, Antagonists,Organophosphate Insecticide Antagonists,Organothiophosphate Insecticide Antagonists,Antagonists, Organophosphate Insecticide,Antagonists, Organothiophosphate Insecticide,Insecticide Antagonists, Organophosphate,Insecticide Antagonists, Organothiophosphate,Reactivators, Cholinesterase
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine

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