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J Fusek - One of the best experts on this subject based on the ideXlab platform.

  • The influence of anticholinergic drug selection on the efficacy of antidotal treatment of soman-poisoned rats.
    Toxicology, 2000
    Co-Authors: J Kassa, J Fusek
    Abstract:

    The influence of some anticholinergic drugs (atropine, Benactyzine, biperiden, scopolamine) on the efficacy of antidotal treatment to eliminate soman (O-pinacolyl methylphosphonofluoridate)-induced disturbance of respiration and circulation and to protect experimental animals poisoned with supralethal dose of soman (1.5 x LD(50)) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. While the oxime HI-6 in combination with atropine prevented soman-induced changes in monitored physiological parameters insufficiently and very shortly, the combination of HI-6 with Benactyzine or biperiden is able to prevent soman-induced alteration of respiration and circulation much more longer. Nevertheless, only rats treated with HI-6 in combination with scopolamine were fully protected against the lethal toxic effects of soman within 2 h following soman challenge. Our findings confirm that anticholinergic drugs with the strong central antimuscarinic activity, such as Benactyzine, biperiden and especially scopolamine, seem to be more effective adjuncts to HI-6 treatment of severe acute soman-induced poisoning than atropine.

  • The positive influence of a cholinergic–anticholinergic pretreatment and antidotal treatment on rats poisoned with supralethal doses of soman
    Toxicology, 1998
    Co-Authors: Jirí Kassa, J Fusek
    Abstract:

    The influence of pretreatment with the drug mixture (pyridostigmine, Benactyzine and trihexyphenidyle), and antidotal treatment (the oxime HI-6 in combination with Benactyzine) on respiration, circulation and survival of experimental animals poisoned with supralethal doses of soman (2 x LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. Untreated soman poisoning caused rapid respiratory depression, progressive bradycardia and a short-term increase in the mean arterial pressure, followed immediately by hypotension. The poisoned rats died on average within 10 min from respiratory and circulatory insufficiency. A cholinergic-anticholinergic pretreatment alone partially prevented changes in monitored physiological variables, caused by soman, but only for a few minutes; post-poisoning treatment with antidotes, also alone, had similar effects. The rats died on average within 30 min from respiratory and circulatory failure. When rats were pretreated by the drug mixture and treated by antidotes, respiration as well as circulation were completely restored and the rats survived at least 120 min following soman challenge. The results of the investigation suggest that cholinergic-anticholinergic pretreatment seems able to enhance the efficacy of antidotal treatment in restoring respiratory and circulatory changes induced by soman.

  • Effect of Panpal pretreatment and antidotal treatment (HI-6 plus Benactyzine) on respiratory and circulatory function in soman-poisoned rats
    Human & experimental toxicology, 1997
    Co-Authors: Jirí Kassa, J Fusek
    Abstract:

    1 The effect of pharmacological pretreatment (pyridostigmine, Benactyzine and trihexyphenidyle), designated Panpal, and antidotal treatment (the oxime HI-6 plus Benactyzine) in soman poisoning was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activity in diaphragm and various brain parts. 3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acetylcholinesterase activity in all brain parts studied. 4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreatment or antidotal treatment alone. 5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman-poisoned rats without significant reactivation of brain acetylcholinesterase.

Gregory Galbicka - One of the best experts on this subject based on the ideXlab platform.

  • Effects of selected anticholinergics on acoustic startle response in rats.
    Journal of Applied Toxicology, 2001
    Co-Authors: Maurice L. Sipos, Vanessa Burchnell, Gregory Galbicka
    Abstract:

    The present study compared the effects of the anticholinergics aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, Benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide and trihexyphenidyl hydrochloride on acoustic startle response in rats. Peak startle amplitude, latency to peak startle amplitude and prepulse inhibition following 100- and 120-dB tones were recorded 15 min following drug administration in food-restricted rats. Aprophen, atropine, azaprophen, Benactyzine, biperiden and scopolamine significantly increased peak startle amplitude and decreased latency to peak startle amplitude following 100-dB pulses. In contrast, only biperiden increased peak startle amplitude following 120-dB pulses, whereas atropine and trihexyphenidyl decreased latency to peak startle amplitude following 120-dB pulses. Benactyzine decreased prepulse inhibition following both 100- and 120-dB pulses, whereas both biperiden and scopolamine decreased prepulse inhibition following 120-dB pulses. Acoustic startle response measures were effective in differentiating the effects of anticholinergic compounds. The comparison of drug effects on the acoustic startle response may be useful in selecting efficacious anticholinergic drug therapies with a minimal range of side-effects. In addition, these data may be useful in down-selecting the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests. Copyright © 2001 John Wiley & Sons, Ltd.

  • Effects of selected anticholinergics on acoustic startle response in rats.
    Journal of applied toxicology : JAT, 2001
    Co-Authors: Maurice L. Sipos, Vanessa Burchnell, Gregory Galbicka
    Abstract:

    The present study compared the effects of the anticholinergics aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, Benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide and trihexyphenidyl hydrochloride on acoustic startle response in rats. Peak startle amplitude, latency to peak startle amplitude and prepulse inhibition following 100- and 120-dB tones were recorded 15 min following drug administration in food-restricted rats. Aprophen, atropine, azaprophen, Benactyzine, biperiden and scopolamine significantly increased peak startle amplitude and decreased latency to peak startle amplitude following 100-dB pulses. In contrast, only biperiden increased peak startle amplitude following 120-dB pulses, whereas atropine and trihexyphenidyl decreased latency to peak startle amplitude following 120-dB pulses. Benactyzine decreased prepulse inhibition following both 100- and 120-dB pulses, whereas both biperiden and scopolamine decreased prepulse inhibition following 120-dB pulses. Acoustic startle response measures were effective in differentiating the effects of anticholinergic compounds. The comparison of drug effects on the acoustic startle response may be useful in selecting efficacious anticholinergic drug therapies with a minimal range of side-effects. In addition, these data may be useful in down-selecting the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests.

  • Dose-response curves and time-course effects of selected anticholinergics on locomotor activity in rats.
    Psychopharmacology, 1999
    Co-Authors: Maurice L. Sipos, Vanessa Burchnell, Gregory Galbicka
    Abstract:

    Rationale: In order to facilitate direct comparisons of anticholinergic drug effects on activity, nine drugs were tested in one laboratory using a standardized procedure. Objective: The present study compared the effects of aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, Benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide, and trihexyphenidyl hydrochloride on activity levels in rats. Methods: Both fine motor activity (reflecting smaller movements) and ambulatory activity (reflecting larger movements) were recorded for 23 h following drug administration in food-restricted rats. All drugs were administered during the light period of the photocycle. Results: Atropine, azaprophen, biperiden, scopolamine, and trihexyphenidyl increased both ambulations and fine motor activity significantly during the first hour post-injection, but the increased activity levels returned to vehicle control levels within 2–6 h post-injection. Benactyzine and procyclidine only increased fine motor activity significantly above vehicle control levels and activity levels returned to vehicle control levels within 2–3 h. Finally, aprophen and diazepam generally did not increase measures of activity significantly above vehicle controls at the dose ranges examined. Conclusions: Based on potencies relative to scopolamine, the potency of the drugs could be ranked as follows: scopolamine > trihexyphenidyl > biperiden > azaprophen > procyclidine > Benactyzine > atropine > aprophen. The comparison of drug effects on activity may be useful in selecting anticholinergic drug therapies with a minimal range of side effects. In addition, these data may reduce the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests.

Jirí Kassa - One of the best experts on this subject based on the ideXlab platform.

  • The influence of oxime and anticholinergic drug selection on the potency of antidotal treatment to counteract acute toxic effects of tabun in mice
    Neurotoxicity Research, 2006
    Co-Authors: Jirí Kassa
    Abstract:

    The influence of newly developed oximes, K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide] and K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide], or currently used oximes (pralidoxime, obidoxime, trimedoxime, HI-6) and anticholinergic drugs (atropine, Benactyzine) on the ability of antidotal treatment to eliminate tabun-induced acute toxic effects was studied in mice. The therapeutical efficacy of trimedoxime and both newly developed oximes (K027, K048) is significantly higher than the potency of pralidoxime (regardless of the choice of anticholinergic drug), obidoxime (in the case of its combination with atropine) and the oxime HI-6 (in the case of its combination with Benactyzine). All studied oximes with the exception of pralidoxime and the oxime HI-6, when combined with Benactyzine, appear to be more efficacious in the elimination of toxic effects of the lethal dose of tabun than their combination with atropine. The findings support the hypothesis that the choice of acetylcholinesterase reactivators as well as the anticholinergic drug selection are important for the effectiveness of an antidotal mixture in the case of antidotal treatment of tabun-induced acute poisonings.

  • The positive influence of a cholinergic–anticholinergic pretreatment and antidotal treatment on rats poisoned with supralethal doses of soman
    Toxicology, 1998
    Co-Authors: Jirí Kassa, J Fusek
    Abstract:

    The influence of pretreatment with the drug mixture (pyridostigmine, Benactyzine and trihexyphenidyle), and antidotal treatment (the oxime HI-6 in combination with Benactyzine) on respiration, circulation and survival of experimental animals poisoned with supralethal doses of soman (2 x LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. Untreated soman poisoning caused rapid respiratory depression, progressive bradycardia and a short-term increase in the mean arterial pressure, followed immediately by hypotension. The poisoned rats died on average within 10 min from respiratory and circulatory insufficiency. A cholinergic-anticholinergic pretreatment alone partially prevented changes in monitored physiological variables, caused by soman, but only for a few minutes; post-poisoning treatment with antidotes, also alone, had similar effects. The rats died on average within 30 min from respiratory and circulatory failure. When rats were pretreated by the drug mixture and treated by antidotes, respiration as well as circulation were completely restored and the rats survived at least 120 min following soman challenge. The results of the investigation suggest that cholinergic-anticholinergic pretreatment seems able to enhance the efficacy of antidotal treatment in restoring respiratory and circulatory changes induced by soman.

  • Effect of Panpal pretreatment and antidotal treatment (HI-6 plus Benactyzine) on respiratory and circulatory function in soman-poisoned rats
    Human & experimental toxicology, 1997
    Co-Authors: Jirí Kassa, J Fusek
    Abstract:

    1 The effect of pharmacological pretreatment (pyridostigmine, Benactyzine and trihexyphenidyle), designated Panpal, and antidotal treatment (the oxime HI-6 plus Benactyzine) in soman poisoning was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activity in diaphragm and various brain parts. 3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acetylcholinesterase activity in all brain parts studied. 4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreatment or antidotal treatment alone. 5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman-poisoned rats without significant reactivation of brain acetylcholinesterase.

Yosef Kapon - One of the best experts on this subject based on the ideXlab platform.

  • Visual and spatial trials paired in a new behavioral procedure: effects of Benactyzine.
    Pharmacology biochemistry and behavior, 1993
    Co-Authors: Ettie Grauer, Yosef Kapon
    Abstract:

    Abstract A paired discrimination (PD) task in which visual and spatial discrimination trials were combined is offered as a method for the evaluation of drug effects on various behavioral parameters. Acquisition of the PD task is characterized by six different parameters simultaneously recorded each session. Analysis of memory requirements suggest that intact reference memory is involved in the performance of both types of trials while working memory is involved only in the performance of the spatial trial. Benactyzine (1–4 mg/kg), an anticholinergic drug, was tested for its effects on visual and spatial tasks presented either separately or in the PD combination. Benactyzine-induced mydriasis was also determined for its possible role in photophobic-induced errors. Benactyzine was found to differentially increase the number of errors performed during the spatial but nor during the visual trials. The data are in accord with earlier finding of specific cholinergic involvement in working memory processes. Thus, low doses of Benactyzine, and the PD task, can prove useful in the cognitive analysis of cholinergic hypofunction and its reversal by memory-enhancing drugs.

Jiří Kassa - One of the best experts on this subject based on the ideXlab platform.

  • Anticholinergic drugs--functional antidotes for the treatment of tabun intoxication.
    Acta medica (Hradec Kralove), 2004
    Co-Authors: Gabriela Krejcova, Jiří Kassa
    Abstract:

    1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun (LD50). The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, Benactyzine, biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. 3. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (Benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine.

  • Anticholinergic Drugs – Functional Antidotes for the Treatment of Tabun Intoxication
    Karolinum Press, 2004
    Co-Authors: Gabriela Krejcova, Jiří Kassa
    Abstract:

    Summary: 1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun (LD50). The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, Benactyzine, biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. 3. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (Benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine

  • The influence of anticholinergic drug and oxime selection on the effectiveness of antidotal treatment against tabun-induced poisoning in mice.
    Acta medica (Hradec Kralove), 2002
    Co-Authors: Jiří Kassa
    Abstract:

    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.

  • The influence of anticholinergic drug selection on the effectiveness of oximes against soman-induced supralethal poisoning in mice.
    Acta medica (Hradec Kralove), 2001
    Co-Authors: Jiří Kassa
    Abstract:

    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 effectiveness of antidotal mixture in the case of prophylactic administration of antidotes.

  • Importance of cholinolytic drug selection for the efficacy of HI-6 against soman in rats
    Toxicology, 1997
    Co-Authors: Jiří Kassa
    Abstract:

    The influence of cholinolytic drugs (atropine, Benactyzine, biperiden) on the efficacy of the oxime HI-6 (1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride monohydrate) on soman-induced anticholinesterase and stressogenic effects was studied in rats. Soman-induced acetylcholinesterase inhibition in blood and diaphragm and the stressogenic effects of soman, i.e. an increase in plasma corticosterone level and liver tyrosine aminotransferase activity, were more significantly diminished by HI-6 in combination with Benactyzine or biperiden in comparison with HI-6 plus atropine. These findings support a hypothesis that Benactyzine as well as biperiden can increase the efficacy of the oxime HI-6 in comparison with atropine. They demonstrate the importance of cholinolytic drug selection in the treatment of soman poisoning in rats.