scholarly journals The Influence of Anticholinergic Drug and Oxime Selection on the Effectiveness of Antidotal Treatment Against Tabun-Induced Poisoning in Mice

2002 ◽  
Vol 45 (2) ◽  
pp. 75-78 ◽  
Author(s):  
Jiří Kassa
Keyword(s):  
Anticholinergic Drug ◽  
Lethal Dose ◽  
Acute Poisoning ◽  
Toxic Effects ◽  
Anticholinergic Drugs ◽  
Drug Selection ◽  
Lethal Effects ◽  
Hi 6 ◽  
The Difference ◽  
Acetylcholinesterase Reactivators

1. The influence of oximes (pralidoxime, obidoxime, HI-6) and anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) on the effectiveness of antidotal treatment to eliminate tabun-induced lethal effects was studied in mice. 2. Obidoxime seems to be the most efficacious oxime for the elimination of tabun-induced lethal effects in mice, although the difference in the efficacy of obidoxime and HI-6 is not significant when they are combined with atropine. 3. Obidoxime and HI-6 when combined with centrally acting anticholinergic drugs (benactyzine, biperiden and scopolamine) seem to be more efficacious in the elimination of toxic effects of the lethal dose of tabun than their combination with atropine. 4. The findings support the hypothesis that the choice of acetylcholinesterase reactivators as well as the anticholinergic drug selection are important for the effectiveness of antidotal mixture in the case of antidotal treatment of tabun-induced acute poisoning.

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.

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 The Influence of Anticholinergic Drug Selection on the Effectiveness of Oximes Against Soman-Induced Supralethal Poisoning in Mice

2001 ◽  
Vol 44 (2) ◽  
pp. 77-79 ◽  
Author(s):  
Jiří Kassa
Keyword(s):  
Anticholinergic Drug ◽  
The Other ◽  
Toxic Effects ◽  
Anticholinergic Drugs ◽  
Drug Selection ◽  
Hi 6 ◽  
Prophylactic Administration ◽  
Other Hand ◽  
Selection For

1. The influence of anticholinergic drugs (atropine, benactyzine, biperiden) on the efficacy of monopyridinium and bispyridinium oximes (HI-6, BI-6, obidoxime, pralidoxime, methoxime) on soman-induced supralethal poisoning was studied in mice. 2. While methoxime combined with benactyzine or biperiden seems to be more efficacious in the elimination of toxic effects of supralethal dose of soman than its combination with atropine, the efficacy of the other oximes studied against soman-induced toxic effects is not significantly influenced by the anticholinergic drug selection. 3. On the other hand, there are big differences in the effectiveness of oximes tested as to their ability to eliminate toxic effects of soman at supralethal doses. 4. The findings support the fact that the choice of acetylcholinesterase reactivator is more important than the anticholinergic drug selection for the effectivenes of antidotal mixture in the case of prophylactic administration of antidotes.

scholarly journals The Influence of the Time of Antidotal Treatment Administration on the Potency of Newly Developed Oximes to Counteract Acute Toxic Effects of Tabun in Mice

2005 ◽  
Vol 48 (2) ◽  
pp. 87-90 ◽  
Author(s):  
Jiří Kassa
Keyword(s):  
Acute Toxicity ◽  
Therapeutic Efficacy ◽  
Anticholinergic Drug ◽  
Acute Poisoning ◽  
Toxic Effects ◽  
Time Interval ◽  
Lethal Effects ◽  
Prolonged Time ◽  
Treatment Administration ◽  
Time Of Administration

1. The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and newly developed oxime (K027 or K048) on its effectiveness to eliminate tabun-induced lethal toxic effects was studied in mice. 2. The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration regardless of the choice of the oxime. 3. Our results show that both oximes studied (K027, K048) are able to sufficiently eliminate lethal effects of tabun. Nevertheless, their efficacy significantly decreases when they were administered 5 min after tabun poisoning. 4. The findings support the hypothesis that both newly developed oximes appear to be suitable oximes to counteract acute toxicity of tabun although their ability to eliminate lethal toxic effects of tabun significantly decreases with prolonged time interval between tabun challenge and antidotal treatment administration.

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.

A Comparison of the Reactivating and Therapeutic Efficacy of Chosen Combinations of Oximes With Individual Oximes Against VX in Rats and Mice

2011 ◽  
Vol 30 (5) ◽  
pp. 562-567 ◽  
Author(s):  
Jiri Kassa ◽  
Jana Zdarova Karasova ◽  
Vendula Sepsova ◽  
Filip Caisberger ◽  
Jiri Bajgar
Keyword(s):  
Acute Toxicity ◽  
Therapeutic Efficacy ◽  
Acute Poisoning ◽  
Hi 6 ◽  
Lethal Toxicity ◽  
The Difference ◽  
Rats And Mice

The ability of 2 combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate VX-inhibited acetylcholinesterase and reduce acute toxicity of VX was compared with the reactivating and therapeutic efficacy of antidotal treatment involving a single oxime (HI-6, trimedoxime, K203) in rats and mice. Our results showed that the reactivating efficacy of both combinations of oximes studied in rats is significantly higher than the reactivating efficacy of all individual oximes in diaphragm and roughly corresponds to the most effective individual oxime in blood and brain. Both combinations of oximes were found to be more effective in the reduction of acute lethal toxicity of VX in mice than the antidotal treatment involving the most efficacious individual oxime although the difference is not significant. Based on the obtained data, we can conclude that the antidotal treatment involving the chosen combinations of oximes brings benefit for the reactivation of VX-inhibited acetylcholinesterase in rats and for the antidotal treatment of VX-induced acute poisoning in mice.

scholarly journals The Influence of Oxime Selection on the Efficacy of Antidotal Treatment of Soman-Poisoned Rats

2002 ◽  
Vol 45 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Jiří Kassa ◽  
Josef Fusek
Keyword(s):  
Rat Model ◽  
The Other ◽  
Toxic Effects ◽  
Experimental Animals ◽  
Hi 6 ◽  
Other Hand ◽  
On Line ◽  
Acetylcholinesterase Reactivators

1. The influence of some acetylcholinesterase reactivators (HI-6, obidoxime, pralidoxime) on the efficacy of antidotal treatment to eliminate soman-induced disturbance of respiration and circulation and to protect experimental animals poisoned with supralethal dose of soman (1.5 × LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2. Obidoxime or pralidoxime in combination with atropine were insufficient to enable soman-poisoned rats to survive for 2 hours when given 1 minute after the administration of soman. 3. On the other hand, the ability of the oxime HI-6 in combination with atropine to prevent soman-induced alteration of respiration and circulation was significantly higher. Some rats treated with HI-6 in combination with atropine were fully protected against the lethal toxic effects of soman within 2 hours following soman administration. 4. Our findings confirm that the oxime HI-6 seems to be a much more suitable and efficacious acetylcholinesterase reactivator for the antidotal treatment of severe acute soman-induced poisoning than currently used obidoxime or pralidoxime.

scholarly journals A Comparison of the Neuroprotective Efficacy of Pharmacological Pretreatment and Antidotal Treatment in Soman-Poisoned Rats

2003 ◽  
Vol 46 (3) ◽  
pp. 101-107 ◽  
Author(s):  
Jiří Kassa ◽  
Gabriela Krejčová ◽  
Ivan Samnaliev
Keyword(s):  
Motor Activity ◽  
Lethal Dose ◽  
Automatic Measurement ◽  
Albino Rats ◽  
Lethal Effects ◽  
Experimental Animals ◽  
Hi 6 ◽  
Neurotoxic Effects ◽  
Neuroprotective Efficacy ◽  
Functional Observational Battery

1. To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. 3. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate somaninduced neurotoxic signs. 4. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.

PRECLINICAL STUDY OF THE VETERINARY DRUGS TOXICITY

1970 ◽  
pp. 61-64
Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov
Keyword(s):  
Lethal Dose ◽  
Clinical Manifestations ◽  
Preclinical Study ◽  
Veterinary Drugs ◽  
Toxic Effects ◽  
Laboratory Animals ◽  
Therapeutic Effects ◽  
Significant Information ◽  
Important Indicator ◽  
Organ Systems

Preclinical study of the drugs toxicity was analysed it allows predicting the safety of veterinary drugs in laboratory animals. The fundamental normative instruments in the field of preclinical study of drugs for veterinary medicine and animal husbandry are Order of the Ministry of Agriculture of the Russian Federation dated 06.03.2018 N 101 and GOST 33044-2014 Principles of Good Laboratory Practice. An important indicator of the preclinical study of the veterinary drugs is the determination (calculation) of median lethal dose value (lethal dose for half of the animals tested) or concentration (LD50 or LC50). Existing methods for determining this indicator make it possible at the initial study stage to determine the degree and class the drug of toxicity. Studying the symptoms of intoxication in the analysis of pharmacological substances one obtains significant information about the nature of the action of the future drug. The clinical manifestations of intoxication with damage to various organ systems are presented. As criteria for assessing the toxic effects of veterinary drugs it is recommended to determine LD50, cumulation coefficient, latitude index of therapeutic effects, dose level of toxic effects in the experiment which allows predicting the nature and degree of toxic effects of the drug even at the stage of preclinical veterinary drugs study.

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