The Reactivating and Therapeutic Efficacy of Oximes to Counteract Russian VX Poisonings

2006 ◽  
Vol 25 (5) ◽  
pp. 397-401 ◽  
Author(s):  
Jiri Kassa ◽  
Daniel Jun ◽  
Kamil Kuca
Keyword(s):  
Therapeutic Efficacy ◽  
Central Compartment ◽  
Toxic Effects ◽  
Peripheral Compartment ◽  
Structural Analogue ◽  
Hi 6 ◽  
Alkyl Groups ◽  
Brain Acetylcholinesterase ◽  
Acute Toxic

Russian VX ( O-isobutyl- S-(2-diethylaminoethyl)methylphosphonothioate) is the structural analogue of VX agent. It differs from VX agent ( O-ethyl- S-(2-diisopropylaminoethyl) methylphosphonothioate) by two alkyl groups. The potency of currently available oximes (pralidoxime, obidoxime, HI-6) to reactivate Russian VX–inhibited acetylcholinesterase and to eliminate Russian VX–induced acute toxic effects was evaluated using in vivo methods. In vivo determined percentage of reactivation of Russian VX–inhibited blood and brain acetylcholinesterase in poisoned rats shows that HI-6 seems to be the most efficacious reactivator of Russian VX–inhibited acetylcholinesterase among currently used oximes in the peripheral compartment, whereas no difference between reactivating efficacy of all tested oximes was observed in the central compartment. The oxime HI-6 was also found to be the most efficacious oxime in the elimination of acute lethal toxic effects in Russian VX–poisoned mice among all studied oximes. Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings.

scholarly journals The Ability of Oxime Mixtures to Increase the Reactivating and Therapeutic Efficacy of Antidotal Treatment of Cyclosarin Poisoning in Rats and Mice

2012 ◽  
Vol 55 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Jiří Kassa ◽  
Jana Zdarová Karasová ◽  
Růžena Pavlíková ◽  
Filip Caisberger ◽  
Jiří Bajgar
Keyword(s):  
Beneficial Effect ◽  
Therapeutic Efficacy ◽  
Acute Poisoning ◽  
Toxic Effects ◽  
Hi 6 ◽  
Rats And Mice

The reactivating and therapeutic efficacy of two combinations of oximes (HI‑6 + trimedoxime and HI‑6 + K203) was compared with the effectiveness of antidotal treatment involving single oxime (HI‑6, trimedoxime, K203) using in vivo methods. In vivo determined percentage of reactivation of cyclosarin‑inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is slightly higher than the reactivating efficacy of the most effective individual oxime in blood, diaphragm as well as in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in cyclosarin‑poisoned mice than the antidotal treatment involving single oxime. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings a beneficial effect for its ability to counteract the acute poisoning with cyclosarin.

scholarly journals The Influence of the Time of Antidotal Treatment Administration on Its Effectiveness Against Tabun-Induced Poisoning in Mice

2004 ◽  
Vol 47 (2) ◽  
pp. 111-114 ◽  
Author(s):  
Jiří Kassa
Keyword(s):  
Acute Toxicity ◽  
Therapeutic Efficacy ◽  
Anticholinergic Drug ◽  
Acute Poisoning ◽  
Toxic Effects ◽  
Lethal Effects ◽  
Hi 6 ◽  
Treatment Administration ◽  
Time Of Administration ◽  
Acute Toxic

1. The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and oxime (pralidoxime, obidoxime, HI-6 or trimedoxime) on its effectiveness to eliminate tabun-induced lethal effects was studied in mice. 2. The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration when obidoxime or the oxime HI-6 was used as an acetylcholinesterase reactivator. 3. Pralidoxime is practically ineffective to eliminate acute toxic effects of tabun regardless of the time of its administration. 4. Our results show that trimedoxime seems to be the most effective to eliminate lethal effects of tabun. In addition, its efficacy does not decrease when it is administered 5 min after tabun poisoning. 5. The findings support the hypothesis that trimedoxime appears to be the most suitable oxime to counteract acute toxicity of tabun because of its ability to eliminate lethal effects of tabun when it is injected 5 min after tabun challenge on the contrary to other oximes tested.

scholarly journals Comparative determination of the efficacy of bispyridinium oximes in paraoxon poisoning / Usporedno određivanje učinkovitosti bispiridinijevih oksima pri trovanju paraoksonom

2015 ◽  
Vol 66 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Suzana Žunec ◽  
Božica Radić ◽  
Kamil Kuča ◽  
Kamil Musilek ◽  
Ana Lucić Vrdoljak
Keyword(s):  
Therapeutic Efficacy ◽  
Standard Therapy ◽  
Organophosphorus Compounds ◽  
Nerve Agents ◽  
Therapeutic Efficiency ◽  
Hi 6 ◽  
Comparative Determination

Abstract The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and nerve agents) motivated us to search for new, more effective oximes. We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD50) combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD50=21.4 mg kg-1) to mice, while monoxime K027 was the least toxic (LD50=672.8 mg kg-1). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD50 of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be antidotes for paraoxon intoxication.

scholarly journals Assessment of the Therapeutic and Anticonvulsive Efficacy of a Drug Combination Consisting of Trihexyphenidyle and HI-6 in Soman-Poisoned Rats

2004 ◽  
Vol 47 (3) ◽  
pp. 171-175
Author(s):  
Jiří Kassa ◽  
Ivan Samnaliev
Keyword(s):  
Drug Combination ◽  
Anticholinergic Drug ◽  
Acute Poisoning ◽  
Toxic Effects ◽  
Anticholinergic Drugs ◽  
Lethal Effects ◽  
Hi 6 ◽  
Acute Toxic

1. The influence of two anticholinergic drugs (atropine, trihexyphenidyle) on the effectiveness of antidotal treatment to eliminate soman-induced lethal effects and convulsions was studied in rats. 2. The oxime HI-6 when combined with centrally acting anticholinergic drug trihexyphenidyle seems to be more efficacious in the elimination of acute toxic effects of soman than its combination with atropine. 3. The findings support the hypothesis that the choice of the anticholinergic drug is important for the effectiveness of antidotal mixture in the case of antidotal treatment of soman-induced acute poisoning.

A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with presently used oximes and H oximes against sarin by in vitro and in vivo methods

1999 ◽  
Vol 18 (9) ◽  
pp. 560-565 ◽  
Author(s):  
J Kassa ◽  
J Cabal
Keyword(s):  
Therapeutic Efficacy ◽  
Hi 6 ◽  
Hlö 7

1 The reactivating and therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-/2-hydroxyiminomethylpyridinium/-4-/carbamoylpyridinium/-2-butene dibromide), against organophosphate sarin was compared with presently used oximes (pralidoxime, obidoxime, methoxime) and H oximes (HI-6, HLö-7) by in vitro and in vivo methods. 2 Our results confirm that the new oxime BI-6 is a significantly more efficacious acetylcholinesterase reactivator than currently available pralidoxime and obidoxime but not as effective as H oximes (HI-6, HLö-7) in vitro as well as in vivo. In addition, the oxime BI-6 is able to protect supralethal sarin poisoned rats at human-relevant doses. 3 Our data also suggest that the potency of oximes tested to reactivate sarin-inhibited acetylcholinesterase in vitro closely corresponds to their reactivating efficacy in vivo and their ability to protect rats poisoned with supralethal doses of sarin.

scholarly journals Protective Effect of Reversible Cholinesterase Inhibitors (Tacrine, Pyridostigmine) and EqBuChE against VX Poisoning and Brain Acetylcholinesterase Inhibition in Rats

2008 ◽  
Vol 51 (4) ◽  
pp. 223-228 ◽  
Author(s):  
Jiří Bajgar
Keyword(s):  
Protective Effect ◽  
Cholinesterase Inhibitors ◽  
Acetylcholinesterase Inhibition ◽  
Prophylactic Effect ◽  
Hi 6 ◽  
Brain Acetylcholinesterase

The protective effect of the reversible cholinesterase inhibitors tacrine and pyridostigmine alone or in combination with different drugs against acetylcholinesterase inhibition in the pontomedullar area and cerebellum of rats caused by VX agent (O-ethyl S-2-diisopropylaminoethyl methyl phosphonothiolate) in vivo (2xLD50) was studied along with survival of animals pretreated with different combinations of the drugs used. The best prophylactic effect was observed in a combination of pyridostigmine with benactyzine, trihexyphenidyle and HI-6. Tacrine alone or in other combinations has had no better prophylactic effect in comparison with these combinations containing pyridostigmine. Equine butyrylcholinesterase, also protected against VX poisoning very effectively.

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