Experts and Doctors on cholinesterase inhibitors in Hradec Králové, Královéhradecký, Czech Republic
Locale: Hradec Králové, Královéhradecký, Czech Republic
Topic: cholinesterase inhibitors
- Pohanka M, Kuca K, Kassa J. New performance of biosensor technology for Alzheimer's disease drugs: in vitro comparison of tacrine and 7-methoxytacrine. Neuro Endocrinol Lett. 2008;29:755-8 pubmed..Our study shows that biosensor technology could be used as a quick and cheap tool for testing of promising AChE inhibitors (AD drug candidates). ..
- Kuca K, Patocka J, Cabal J, Jun D. Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes. Neurotox Res. 2004;6:565-70 pubmed..Rat brain AChE was used as the appropriate source of the enzyme. Our results confirm that there is no single broad-spectrum oxime suitable for the treatment of poisoning with all highly toxic organophosphorus agents. ..
- Kuca K, Jun D, Bajgar J. Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro. Drug Chem Toxicol. 2007;30:31-40 pubmed..Moreover, oxime HI-6 (the most effective one) was not able to reactivate tabun- and soman-inhibited AChE. Due to this fact, it could be designated as a partially broad-spectrum reactivator...
- Pohanka M, Adam V, Kizek R. An acetylcholinesterase-based chronoamperometric biosensor for fast and reliable assay of nerve agents. Sensors (Basel). 2013;13:11498-506 pubmed publisher..The assay was reliable, with minor interferences caused by the organic solvents ethanol, methanol, isopropanol and acetonitrile. Isopropanol was chosen as suitable medium for processing lipophilic samples. ..
- Kuca K, Cabal J, Jung Y, Musilek K, Soukup O, Jun D, et al. Reactivation of human brain homogenate cholinesterases inhibited by Tabun using newly developed oximes K117 and K127. Basic Clin Pharmacol Toxicol. 2009;105:207-10 pubmed publisher..Due to this, experiments on human tissue should be conducted after in vitro and in vivo tests on animals to eliminate such important failures of promising oximes...
- Bajgar J. Protective effect of reversible cholinesterase inhibitors (tacrine, pyridostigmine) and eqbuche against VX poisoning and brain acetylcholinesterase inhibition in rats. Acta Medica (Hradec Kralove). 2008;51:223-8 pubmed..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. ..
- Cabal J, Bajgar J, Kassa J. Evaluation of flow injection analysis for determination of cholinesterase activities in biological material. Chem Biol Interact. 2010;187:225-8 pubmed publisher..The method is simple and not expensive, allowing automatic determination of AChE activity in discrete or continual samples in vitro or in vivo. It will be evaluated for further research of cholinesterase inhibitors. ..
- Cahlíková L, Opletal L, Kurfürst M, Macakova K, Kulhánková A, Hostálková A. Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Chelidonium majus (Papaveraceae). Nat Prod Commun. 2010;5:1751-4 pubmed..The most active of the naturally-occurring alkaloids was chelidonine, which inhibited both HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 26.8 +/- 1.2 microM and 31.9 +/- 1.4 microM, respectively...
- Kassa J. Therapeutic and neuroprotective efficacy of pharmacological pretreatment and antidotal treatment of acute tabun or soman poisoning with the emphasis on pretreatment drug PANPAL. Arh Hig Rada Toksikol. 2006;57:427-34 pubmed
- Kassa J, Kunesova G. The benefit of combination of oximes for the neuroprotective efficacy of antidotal treatment of sarin-poisoned rats. Toxicol Mech Methods. 2012;22:260-7 pubmed publisher..Thus, both tested combinations of oximes in combination with atropine bring a small benefit for the neuroprotective efficacy of antidotal treatment of acute sarin poisonings...
- Kuca K, Cabal J, Jun D, Hrabinova M. Potency of five structurally different acetylcholinesterase reactivators to reactivate human brain cholinesterases inhibited by cyclosarin. Clin Toxicol (Phila). 2007;45:512-5 pubmed..Moreover, according to the results, we can describe basic structural requirements, which are necessary for the efficacious reactivation process...
- Kassa J. [The effect of pharmacologic prophylaxis with Panpal on acetylcholinesterase activity in the diaphragm and various parts of the brain in rats during treated and untreated Soman poisoning]. Cas Lek Cesk. 1998;137:299-302 pubmed
- Kassa J. [Comparison of the effect of HI-6 oxime and its derivatives in combination with benactyzine on cholinergic and stress effects of soman in rats]. Ceska Slov Farm. 1996;45:149-53 pubmed
- Musilek K, Holas O, Kuca K, Jun D, Dohnal V, Opletalova V, et al. Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase. J Enzyme Inhib Med Chem. 2008;23:70-6 pubmed..The best results were obtained for bisquaternary substances with at least one oxime group in position four. ..
- Bajgar J, Hajek P, Zdarova J, Kassa J, Paseka A, Slizova D, et al. A comparison of tabun-inhibited rat brain acetylcholinesterase reactivation by three oximes (HI-6, obidoxime, and K048) in vivo detected by biochemical and histochemical techniques. J Enzyme Inhib Med Chem. 2010;25:790-7 pubmed publisher..AChE activity in the pontomedullar area and frontal cortex seems to be the most important for the therapeutic effect of the reactivators. HI-6 was not a good reactivator for the treatment of tabun intoxication...
- Kassa J, Karasova J, Pavlikova R, Musilek K, Kuca K, Bajgar J, et al. A comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator KR-22934 with the oxime K203 and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice. Toxicol Mech Methods. 2011;21:241-5 pubmed publisher
- Kuca K, Cabal J. [In vitro reactivation of acetylcholinesterase inhibition by O-isopropylmethylfluorophosphonate using the bisquarternary oxime, HS-6]. Ceska Slov Farm. 2004;53:93-5 pubmed..The oxime HS-6 was an effective reactivator of sarin-inhibited AChE. It is not as effective as the H-oxime HI-6, but it is better than 2-PAM and obidoxime...
- Cahlíková L, Zavadil S, Macakova K, Valterova I, Kulhánková A, Host álková A, et al. Isolation and cholinesterase activity of Amaryllidaceae alkaloids from Nerine bowdenii. Nat Prod Commun. 2011;6:1827-30 pubmed..8 +/- 1.1 microg/mL). Belladine inhibited HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 781 +/- 12.5 microM and 284.8 +/-4.2 microM, respectively. ..
- Kassa J, Cabal J. A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with currently available oximes and H oximes against soman by in vitro and in vivo methods. Toxicology. 1999;132:111-8 pubmed
- Pohanka M. Acetylcholinesterase inhibitors: a patent review (2008 - present). Expert Opin Ther Pat. 2012;22:871-86 pubmed publisher..The research for drugs for Alzheimer's disease needs to focus on inhibitors that reduce the deposition of amyloid plaques, but do not initiate AChE expression. ..
- Soukup O, Jun D, Tobin G, Kuca K. The summary on non-reactivation cholinergic properties of oxime reactivators: the interaction with muscarinic and nicotinic receptors. Arch Toxicol. 2013;87:711-9 pubmed publisher..Even though atropine showed a much higher muscarinic antagonism, it is supposed that non-reactivation properties of oxime reactivators play a significant role in the treatment of OP poisoning. ..
- Kassa J, Karasova J, Musilek K, Kuca K, Jung Y. A comparison of the therapeutic and reactivating efficacy of newly developed oximes (K117, K127) and currently available oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice. Drug Chem Toxicol. 2008;31:371-81 pubmed
- Kassa J, Bajgar J. The influence of pharmacological pretreatment on efficacy of HI-6 oxime in combination with benactyzine in soman poisoning in rats. Hum Exp Toxicol. 1996;15:383-8 pubmed..4. These findings confirm that PANPAL prophylaxis can improve prognosis of soman poisoning especially by protection of cholinesterases. ..
- Kuca K, Cabal J, Kassa J. A comparison of the efficacy of a bispyridinium oxime--1,4-bis-(2-hydroxyiminomethylpyridinium) butane dibromide and currently used oximes to reactivate sarin, tabun or cyclosarin-inhibited acetylcholinesterase by in vitro methods. Pharmazie. 2004;59:795-8 pubmed..Thus, oxime K033 seems to be a relatively efficacious broad spectrum acetylcholinesterase reactivator and, therefore, could be useful if no information about the type of nerve agent used was available. ..
- Musilek K, Jun D, Cabal J, Kassa J, Gunn Moore F, Kuca K. Design of a potent reactivator of tabun-inhibited acetylcholinesterase--synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). J Med Chem. 2007;50:5514-8 pubmed
- Kuca K, Kassa J. In vitro reactivation of acetylcholinesterase using the oxime K027. Vet Hum Toxicol. 2004;46:15-8 pubmed..HI-6 is currently regarded the most promising reactivator of organophosphates-inhibited AChE...
- Kuca K, Cabal J, Jun D, Hrabinova M. In vitro evaluation of acetylcholinesterase reactivators as potential antidotes against tabun nerve agent poisonings. Drug Chem Toxicol. 2006;29:443-9 pubmed..In most cases, the reactivation bell-shaped curve is obtained. The most potent AChE reactivators are selected and provided for further experiments during our development process...
- Kassa J. [Importance of reactivation of fosdrin-inhibited acetylcholinesterase in the brain and diaphragm for the in vivo therapeutic effect of oximes in rats poisoned with fosdrin]. Cas Lek Cesk. 2000;139:237-9 pubmed
- Sevelová L, Vachek J. Effect of methoxime combined with anticholinergic, anticonvulsant or anti-HCN drugs in tabun-poisoned mice. Acta Medica (Hradec Kralove). 2003;46:109-12 pubmed..We established that anticholinergic drug option in the therapeutic mixture of methoxime and anticholinergic drug did not cause the difference in the antidotal treatment effectivities. ..
- Komloova M, Musilek K, Horova A, Holas O, Dohnal V, Gunn Moore F, et al. Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors--implications for early myasthenia gravis treatment. Bioorg Med Chem Lett. 2011;21:2505-9 pubmed publisher..A molecular modelling study further confirmed its binding to the peripheral active site of hAChE via apparent ?-? or ?-cationic interactions...
- Kassa J. [Comparison of the effect of selected cholinesterase reactivators combined with atropine on soman and fosdrin toxicity in mice]. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl. 1995;38:63-6 pubmed..These findings suggest that HI-6 has definite advantage over obidoxime as well as tetroxime in the treatment of poisoning with not only highly toxic organophosphates but also organophoshorus insecticides. ..
- Jun D, Musilova L, Kuca K, Kassa J, Bajgar J. Potency of several oximes to reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by paraoxon in vitro. Chem Biol Interact. 2008;175:421-4 pubmed publisher..In the case of BuChE, none of these reactivators could be used for its reactivation. ..
- Musilek K, Kucera J, Jun D, Dohnal V, Opletalova V, Kuca K. Monoquaternary pyridinium salts with modified side chain-synthesis and evaluation on model of tabun- and paraoxon-inhibited acetylcholinesterase. Bioorg Med Chem. 2008;16:8218-23 pubmed publisher..However, extensive differences were found by a SAR study for various side chains on the non-oxime part of the reactivator molecule. ..
- Pohanka M, Jun D, Kuca K. In vitro reactivation of trichlorfon-inhibited butyrylcholinesterase using HI-6, obidoxime, pralidoxime and K048. J Enzyme Inhib Med Chem. 2009;24:680-3 pubmed publisher..There was also an observed lowering of reactivation efficacy when butyrylcholinesterase was exposed to trichlorfon for a longer time interval...
- Kassa J. [Comparison of the effects of BI-6, a new asymmetric bipyridine oxime, with HI-6 oxime and obidoxime in combination with atropine on soman and fosdrine toxicity in mice]. Ceska Slov Farm. 1999;48:44-7 pubmed..At the equi-effective level which respects the toxicity of the oxime and is therefore more important for practical use, it is a therapeutically weaker reactivator of acetylcholinesterase than HI-6. ..
- Krejcova G, Kassa J. Acute experimental tabun-induced intoxication and its therapy in rats. Cent Eur J Public Health. 2004;12 Suppl:S48-52 pubmed
- Kuca K, Musilek K, Jun D, Pohanka M, Ghosh K, Hrabinova M. Oxime K027: novel low-toxic candidate for the universal reactivator of nerve agent- and pesticide-inhibited acetylcholinesterase. J Enzyme Inhib Med Chem. 2010;25:509-12 pubmed publisher..In the case of cyclosarin- and soman-inhibited AChE, oxime K027 did not reach sufficient reactivation potency. ..
- Musilek K, Komloova M, Holas O, Hrabinova M, Pohanka M, Dohnal V, et al. Preparation and in vitro screening of symmetrical bis-isoquinolinium cholinesterase inhibitors bearing various connecting linkage--implications for early Myasthenia gravis treatment. Eur J Med Chem. 2011;46:811-8 pubmed publisher..Two newly prepared compounds were also chosen for docking studies that confirmed apparent ?-? or ?-cationic interactions aside the cholinesterases catalytic sites. The SAR findings were discussed. ..
- Kassa J, Krejcova G, Samnaliev I. A comparison of the neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in soman-poisoned rats. Acta Medica (Hradec Kralove). 2003;46:101-7 pubmed..The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL. ..
- Kassa J, Koupilová M. Neuroprotective effects of antidotes in soman-poisoned rats. Acta Medica (Hradec Kralove). 1999;42:127-31 pubmed
- Bartosova L, Bielavska M, Bajgar J. Detection of sarin in plasma of rats after inhalation intoxication. J Enzyme Inhib Med Chem. 2006;21:509-14 pubmed
- Musilek K, Holas O, Kuca K, Jun D, Dohnal V, Opletalova V, et al. Novel series of bispyridinium compounds bearing a (Z)-but-2-ene linker--synthesis and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. Bioorg Med Chem Lett. 2007;17:3172-6 pubmed..Notably, the oxime group in position four substantially increased the ability of the novel compounds to reactivate paraoxon-inhibited AChE. ..
- Kassa J, Korabecny J, Nepovimova E. The Evaluation of Benefit of Newly Prepared Reversible Inhibitors of Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological Pretreatment of Soman-Poisoned Mice. Acta Medica (Hradec Kralove). 2017;60:37-43 pubmed publisher..These findings demonstrate that pharmacological pretreatment of somanpoisoned mice can be promising and useful in the case of administration of 6-chlorotacrine and partly compound 2. ..
- Cahlíková L, Benesová N, Macakova K, Urbanová K, Opletal L. GC/MS analysis of three Amaryllidaceae species and their cholinesterase activity. Nat Prod Commun. 2011;6:1255-8 pubmed..Eleven alkaloids were identified by GC/MS. Significant cholinesterase inhibitory activity was demonstrated by the alkaloid extract of N. undulata (IC50,(HuAChE) = 14.3 +/- 1.2 microg/mL; IC50,(HuBuChE) = 33.9 +/- 1.9 microg/mL)...
- Kassa J. Importance of cholinolytic drug selection for the efficacy of HI-6 against soman in rats. Toxicology. 1997;116:147-52 pubmed..They demonstrate the importance of cholinolytic drug selection in the treatment of soman poisoning in rats. Ltd. ..
- Bartosova L, Kuca K, Jun D, Kunesova G. Bispyridinium oximes as antidotal treatment of cyclosarin poisoning-in vitro and in vivo testing. Int J Toxicol. 2005;24:399-402 pubmed..The HI-6 oxime appeared to be the most effective oxime in vitro and in vivo...
- Kuca K, Patocka J. Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium--oximes. J Enzyme Inhib Med Chem. 2004;19:39-43 pubmed
- Sevelová L, Bajgar J, Saxena A, Doctor B. Protective effect of equine butyrylcholinesterase in inhalation intoxication of rats with sarin: determination of blood and brain cholinesterase activities. Inhal Toxicol. 2004;16:531-6 pubmed
- Kuca K, Jun D. Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes. J Med Toxicol. 2006;2:141-6 pubmed..Organophosphorus nerve agents inhibit the enzyme, acetylcholinesterase (AChE; EC 188.8.131.52). AChE reactivators (also known as oximes) are generally used for the reactivation of an inhibited enzyme...
- Kassa J, Karasova J, Caisberger F, Musilek K, Kuca K, Jung Y. A comparison of reactivating and therapeutic efficacy of the oxime K203 and its fluorinated analog (KR-22836) with currently available oximes (obidoxime, trimedoxime, HI-6) against tabun in rats and mice. J Enzyme Inhib Med Chem. 2010;25:480-4 pubmed publisher
- Kuca K, Juna D, Musilek K. Structural requirements of acetylcholinesterase reactivators. Mini Rev Med Chem. 2006;6:269-77 pubmed..It is shown that there are several structural fragments possibly involving in the structure of proposed AChE reactivators. Finally, an attempt of a future course of new AChE reactivators development is discussed. ..
- Kassa J, Kuca K, Cabal J. A comparison of the potency of trimedoxime and other currently available oximes to reactivate tabun-inhibited acetylcholinesterase and eliminate acute toxic effects of tabun. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005;149:419-23 pubmed..The oxime HI-6, so efficacious against soman, does not seem to be sufficiently effective oxime to reactivate tabun-inhibited acetylcholinesterase and to counteract acute lethal effects of tabun...
- Kuca K, Cabal J, Kassa J, Jun D, Hrabinova M. In vitro potency of H oximes (HI-6, HLö-7), the oxime BI-6, and currently used oximes (pralidoxime, obidoxime, trimedoxime) to reactivate nerve agent-inhibited rat brain acetylcholinesterase. J Toxicol Environ Health A. 2006;69:1431-40 pubmed..More than one oxime may be necessary for the antidotal treatment of nerve agent-exposed individuals...
- Kassa J, Jun D, Kuca K. The reactivating and therapeutic efficacy of oximes to counteract Russian VX poisonings. Int J Toxicol. 2006;25:397-401 pubmed..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...
- Kuca K, Cabal J, Jun D, Musilek K. In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075--to reactivate tabun-inhibited human brain cholinesterases. Neurotox Res. 2007;11:101-6 pubmed..A second AChE reactivator, K075, does not attain as great a reactivation potency as K074, although its maximal reactivation (17%) was achieved at relevant concentrations for humans...
- Kassa J, Karasova J, Musilek K, Kuca K. An evaluation of therapeutic and reactivating effects of newly developed oximes (K156, K203) and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice. Toxicology. 2008;243:311-6 pubmed
- Kassa J, Humlicek V. A comparison of the potency of newly developed oximes (K074, K075) and currently available oximes (obidoxime, trimedoxime, HI-6) to counteract acute toxic effects of tabun and cyclosarin in mice. Drug Chem Toxicol. 2008;31:127-35 pubmed
- Jun D, Kuca K, Picha J, Koleckar V, Marek J. Potency of novel oximes to reactivate sarin inhibited human cholinesterases. Drug Chem Toxicol. 2008;31:1-9 pubmed..Due to this, in future, only bisquaternary compounds derived from HI-6 or obidoxime should be designed as new potential cholinesterase reactivators...
- Bajgar J. Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication. Acta Medica (Hradec Kralove). 2010;53:207-11 pubmed..Possible way to solve the problem of universal reactivator could be the use of two reactivators. Three chambered autoinjector is an ideal device for this purpose. ..
- Musilova L, Kuca K, Jung Y, Jun D. In vitro oxime-assisted reactivation of paraoxon-inhibited human acetylcholinesterase and butyrylcholinesterase. Clin Toxicol (Phila). 2009;47:545-50 pubmed publisher..In this work, we have evaluated only reactivation of paraoxon-inhibited cholinesterases. To get better understanding of this problem, a larger number of organophosphorus inhibitors should be used. ..