obidoxime chloride


Summary: Cholinesterase reactivator occurring in two interchangeable isomeric forms, syn and anti.

Top Publications

  1. Maxwell D, Brecht K, Koplovitz I, Sweeney R. Acetylcholinesterase inhibition: does it explain the toxicity of organophosphorus compounds?. Arch Toxicol. 2006;80:756-60 pubmed
  2. 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...
  3. Øydvin O, Tansø R, Aas P. Pre-junctional effects of oximes on [3H]-acetylcholine release in rat hippocampal slices during soman intoxication. Eur J Pharmacol. 2005;516:227-34 pubmed
    ..HLö-7 is of particular interest in view of its ability to additionally improve reactivation of the acetylcholinesterase activity...
  4. Grossmüller M, Antony J, Tränkle C, Holzgrabe U, Mohr K. Allosteric site in M2 acetylcholine receptors: evidence for a major conformational change upon binding of an orthosteric agonist instead of an antagonist. Naunyn Schmiedebergs Arch Pharmacol. 2006;372:267-76 pubmed
    ..We conclude that the common allosteric site is still present in OxoM-liganded M2 receptors, but its spatial conformation is considerably altered compared with NMS-liganded receptors...
  5. Maxwell D, Koplovitz I, Worek F, Sweeney R. A structure-activity analysis of the variation in oxime efficacy against nerve agents. Toxicol Appl Pharmacol. 2008;231:157-64 pubmed publisher
  6. 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...
  7. Collange B, Wheelock C, Rault M, Mazzia C, Capowiez Y, Sanchez Hernandez J. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris. Environ Pollut. 2010;158:2266-72 pubmed publisher
  8. Karade H, Raviraju G, Acharya B, Valiveti A, Bhalerao U, Acharya J. Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE). Bioorg Med Chem. 2016;24:4171-4176 pubmed publisher
    ..The acid dissociation constant and IC50 values of these oximes were determined and correlated with the observed reactivation potential. ..
  9. Vos E, Hens J, Lau H, Boon E, Bartelink A. [Poisoning with organophosphate compounds]. Ned Tijdschr Geneeskd. 2002;146:34-7 pubmed
    ..The treatment of these potentially severe intoxications includes rapid decontamination and the administration of high doses of atropine followed by obidoxime. Mechanical ventilation and circulatory support are also indicated...

More Information

Publications103 found, 100 shown here

  1. Peter J, Moran J, Graham P. Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques. Crit Care Med. 2006;34:502-10 pubmed
    ..The status of oximes in human organophosphate poisoning is controversial. This analysis compares the outcomes of therapy with or without oximes...
  2. Antonijevic B, Stojiljkovic M. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin Med Res. 2007;5:71-82 pubmed
    ..Since there are no reports of controlled clinical trials on the use of TMB-4 in human organophosphate pesticide poisoning, LüH-6 may be a better option...
  3. 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
  4. Sabbe M, Desruelles D, Lissens W. Is beta-glucuronidase a clinical useful biomarker for an acute organophosphorus poisoning?. Hum Exp Toxicol. 2008;27:431-3 pubmed publisher
    ..These findings do not support the hypothesis that beta-glucuronidase is a useful biomarker for acute organophosphorus poisoning in humans. ..
  5. Kuca K, Cabal J, Kassa J, Jun D, Hrabinova M. Comparison of in vitro potency of oximes (pralidoxime, obidoxime, HI-6) to reactivate sarin-inhibited acetylcholinesterase in various parts of pig brain. J Appl Toxicol. 2005;25:271-6 pubmed
  6. Acharya J, Dubey D, Raza S. In vitro evaluation of bis-pyridinium oximes bearing methoxy alkane linker as reactivators of sarin inhibited human acetylcholinesterase. Toxicol In Vitro. 2010;24:1797-802 pubmed publisher
    ..Overall, the study reveals that the oxime 4P-2 may have therapeutic potential in the reactivation of human AChE inhibited by sarin. ..
  7. Joosen M, van der Schans M, van Helden H. Percutaneous exposure to the nerve agent VX: Efficacy of combined atropine, obidoxime and diazepam treatment. Chem Biol Interact. 2010;188:255-63 pubmed publisher
    ..In conclusion, percutaneous VX poisoning showed to be effectively treatable when diagnosed on time and when continued over the entire period of time during which VX, in case of ineffective decontamination, penetrates the skin. ..
  8. Snider T, Babin M, Jett D, Platoff G, Yeung D. Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig. J Toxicol Sci. 2016;41:511-21 pubmed publisher
    ..Against PHO, all performed better than 2-PAM Cl. MMB4 DMS was the most effective oxime as it was the only oxime with ED90 < 149 µmol/kg against all three topical OPs tested. ..
  9. Niessen K, Seeger T, Rappenglück S, Wein T, Hofner G, Wanner K, et al. In vitro pharmacological characterization of the bispyridinium non-oxime compound MB327 and its 2- and 3-regioisomers. Toxicol Lett. 2018;293:190-197 pubmed publisher
    ..Thus, more effective drugs have to be developed. Nevertheless, the combination of the methods presented is an effective tool for clarifying structure-activity relationships. ..
  10. Kassa J, Jun D, Kuca K. A comparison of reactivating efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in cyclosarin-and tabun-poisoned rats. J Enzyme Inhib Med Chem. 2007;22:297-300 pubmed
  11. 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. ..
  12. Krejcova G, Kassa J. Neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in tabun-poisoned rats. Toxicology. 2003;185:129-39 pubmed
  13. Herkenhoff S, Szinicz L, Rastogi V, Cheng T, DeFrank J, Worek F. Effect of organophosphorus hydrolysing enzymes on obidoxime-induced reactivation of organophosphate-inhibited human acetylcholinesterase. Arch Toxicol. 2004;78:338-43 pubmed
    ..In conclusion, OPH may be a valuable contribution to the therapeutic regimen against OP poisoning by accelerating the degradation of both the parent compound, OP, and the reaction product, POX. ..
  14. Thiermann H, Szinicz L, Eyer P, Zilker T, Worek F. Correlation between red blood cell acetylcholinesterase activity and neuromuscular transmission in organophosphate poisoning. Chem Biol Interact. 2005;157-158:345-7 pubmed
    ..Accordingly, RBC-AChE appears to be a suitable parameter for judgment of oxime effectiveness at the neuromuscular junction, one of the most important targets for therapy where atropine is ineffective in OP-poisoning. ..
  15. Musilek K, Holas O, Kuca K, Jun D, Dohnal V, Dolezal M. Synthesis of a novel series of non-symmetrical bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. J Enzyme Inhib Med Chem. 2007;22:425-32 pubmed
    ..Seven compounds were promising against paraoxon-inhibited AChE. Two compounds were found to be more potent against tabun-inhibited AChE than obidoxime at a concentration applicable in vivo. ..
  16. Fisar Z, Hroudova J, Korabecny J, Musilek K, Kuca K. In vitro effects of acetylcholinesterase reactivators on monoamine oxidase activity. Toxicol Lett. 2011;201:176-80 pubmed publisher
    ..Because oximes concentrations effective for MAO inhibition could not be achieved in vivo at the cerebral level, we suppose that oximes investigated do not interfere with brain MAO at therapeutically relevant concentrations. ..
  17. 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...
  18. Lorke D, Hasan M, Nurulain S, Kuca K, Schmitt A, Petroianu G. Efficacy of two new asymmetric bispyridinium oximes (K-27 and K-48) in rats exposed to diisopropylfluorophosphate: comparison with pralidoxime, obidoxime, trimedoxime, methoxime, and HI-6. Toxicol Mech Methods. 2009;19:327-33 pubmed publisher
    ..05). Conclusion. Our data provide further evidence that K-27 is a very promising candidate for the treatment of intoxication with a broad spectrum of OPCs...
  19. Stefanovic D, Antonijevic B, Bokonjic D, Stojiljkovic M, Milovanovic Z, Nedeljkovic M. Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos. Basic Clin Pharmacol Toxicol. 2006;98:173-80 pubmed
    ..Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine...
  20. Musilek K, Hambalek J, Holas O, Dohnal V, Kuca K. Monooxime Bispyridinium Reactivators Bearing Xylene Linker Synthesis and In Vitro Evaluation on Model of Organophosphate-Inhibited Acetylcholinesterase. Med Chem. 2016;12:362-70 pubmed
    ..Though the novel reactivators did not exceed previously known compounds, they confirmed former SAR findings for xylene-linked AChE reactivators. ..
  21. Gralewicz S. [Possible consequences of acetylcholinesterase inhibition in organophosphate poisoning. Discussion continued]. Med Pr. 2006;57:291-302 pubmed
    ..This results in overexpression of nonenzymatic AChE functions. It is likely that this overexpression is responsible for at least some of the persistent alterations in the CNS functions which may develop after an OP exposure. ..
  22. 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
  23. 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
  24. Moyer R, McGarry K, Babin M, Platoff G, Jett D, Yeung D. Kinetic analysis of oxime-assisted reactivation of human, Guinea pig, and rat acetylcholinesterase inhibited by the organophosphorus pesticide metabolite phorate oxon (PHO). Pestic Biochem Physiol. 2018;145:93-99 pubmed publisher
    ..3) The therapeutic window for oxime administration following exposure to phorate (or PHO) is not limited by aging. ..
  25. Jokanovic M, Maksimovic M. A comparison of trimedoxime, obidoxime, pralidoxime and HI-6 in the treatment of oral organophosphorus insecticide poisoning in the rat. Arch Toxicol. 1995;70:119-23 pubmed
    ..Trimedoxime was the most effective oxime in the treatment of insecticide poisoning, being successful especially at the lowest tested doses...
  26. Sharma R, Gupta P, Mazumder A, Dubey D, Ganesan K, Vijayaraghavan R. A quantitative NMR protocol for the simultaneous analysis of atropine and obidoxime in parenteral injection devices. J Pharm Biomed Anal. 2009;49:1092-6 pubmed publisher
    A rapid selective and accurate quantitative (1)H NMR method was developed for the simultaneous analysis of obidoxime chloride and atropine sulfate, the active components in parenteral injection devices (PID) used for the emergency ..
  27. Antonijevic B, Stojiljkovic M, Bokonjic D, Vucinić S. [Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos]. Vojnosanit Pregl. 2011;68:1033-40 pubmed
    ..Memantine potentiated the antidotal effect of HI-6 against a lethal dose of soman, as well as the ability of obidoxime to antagonize the toxic effects of dichlorvos and heptenophos probably partly due to its anticonvulsive properties. ..
  28. Eckert S, Eyer P, Herkert N, Bumm R, Weber G, Thiermann H, et al. Comparison of the oxime-induced reactivation of erythrocyte and muscle acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity. Biochem Pharmacol. 2008;75:698-703 pubmed
    ..004 min(-1) and 0.166+/-0.008 min(-1), respectively). The reactivation rate constants of erythrocyte and muscular acetylcholinesterase differed only slightly, highlighting erythrocyte acetylcholinesterase as a proper surrogate marker. ..
  29. Steinritz D, Eyer F, Worek F, Thiermann H, John H. Repetitive obidoxime treatment induced increase of red blood cell acetylcholinesterase activity even in a late phase of a severe methamidophos poisoning: A case report. Toxicol Lett. 2016;244:121-123 pubmed publisher
    ..A repetitive and prolonged administration of obidoxime should be considered in cases of severe methamidophos poisoning and should be tailored with an advanced analytical biomonitoring. ..
  30. Worek F, Herkert N, Koller M, Thiermann H, Wille T. Application of a dynamic in vitro model with real-time determination of acetylcholinesterase activity for the investigation of tabun analogues and oximes. Toxicol In Vitro. 2015;30:514-20 pubmed publisher
  31. Worek F, Thiermann H, Szinicz L. Reactivation and aging kinetics of human acetylcholinesterase inhibited by organophosphonylcholines. Arch Toxicol. 2004;78:212-7 pubmed
  32. Kassa J, Karasova J. A comparison of the potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to counteract tabun-induced neurotoxicity in rats. Toxicology. 2007;229:136-44 pubmed
    ..Due to their neuroprotective effects, both newly developed oximes (especially K075) appear to be more suitable oximes for the antidotal treatment of acute tabun poisonings than the oxime HI-6. ..
  33. Maxwell D, Brecht K, Sweeney R. A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds. Chem Biol Interact. 2013;203:72-6 pubmed publisher
  34. Candiotti K. Correction to: A primer on nerve agents: what the emergency responder, anesthesiologist, and intensivist needs to know. Can J Anaesth. 2018;65:141-142 pubmed publisher
    ..Also in the same row, the third column should read: "Individual doses should not exceed 2 g". The publisher apologizes most sincerely for this error. ..
  35. Grasshoff C, Thiermann H, Gillessen T, Zilker T, Szinicz L. Internal standard high-performance liquid chromatography method for the determination of obidoxime in urine of organophosphate-poisoned patients. J Chromatogr B Biomed Sci Appl. 2001;753:203-8 pubmed
    ..Accuracy was 95.9% in the LOQ range. Using this method, we were able to quantify obidoxime in urine of an organophosphate poisoned patient. Based on this data we calculated that 58% of the administered dose was excreted in the urine. ..
  36. Sakurada K, Ikegaya H, Ohta H, Akutsu T, Takatori T. Hydrolysis of an acetylthiocholine by pralidoxime iodide (2-PAM). Toxicol Lett. 2006;166:255-60 pubmed
    ..It is clear that oximes easily hydrolyze ASCh. We therefore strongly caution that the method of determining AChE activity with ASCh is not suitable for examining the effects of oximes. ..
  37. Thiermann H, Zilker T, Eyer F, Felgenhauer N, Eyer P, Worek F. Monitoring of neuromuscular transmission in organophosphate pesticide-poisoned patients. Toxicol Lett. 2009;191:297-304 pubmed publisher
    ..One-week later, neuromuscular transmission may be largely normal and patients could be weaned from the respirator if other complications are not withstanding. ..
  38. Worek F, Reiter G, Eyer P, Szinicz L. Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates. Arch Toxicol. 2002;76:523-9 pubmed
    ..The results show marked differences among the species, depending on the inhibitor and on the oxime, and indicate that the findings from animal experiments need careful evaluation before extrapolating these data to humans...
  39. Qiu Z, Zhao D, Shi Y, Huang S. [Study on the therapeutic effect of combined use of obidoxime and atropine with respiratory machine on respiratory muscle paralysis caused by omethoate poisoning of rats]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2002;20:359-61 pubmed
    ..To examine the therapeutic effect of combined use of obidoxime and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats...
  40. Bajgar J, Fusek J, Bartosova L, Jun D, Kuca K. Evaluation of reactivation test in anaesthetized dogs with experimental intoxication with nerve agents. J Appl Toxicol. 2006;26:439-43 pubmed
    ..Thus, the reactivation efficacy of obidoxime during nerve agent intoxication indicates that its repeated administration could be easily monitored using the reactivation test...
  41. Worek F, Aurbek N, Koller M, Becker C, Eyer P, Thiermann H. Kinetic analysis of reactivation and aging of human acetylcholinesterase inhibited by different phosphoramidates. Biochem Pharmacol. 2007;73:1807-17 pubmed
  42. Kassa J, Karasova J, Bajgar J, Kuca K, Musilek K, Kopelikova I. A comparison of the reactivating and therapeutic efficacy of newly developed bispyridinium oximes (K250, K251) with commonly used oximes against tabun in rats and mice. J Enzyme Inhib Med Chem. 2009;24:1040-4 pubmed publisher
  43. Ben Haim S, Ben Ami H, Hayam G, Taitelman U, Edoute Y. Effect of phosphamidon and obidoxime on the QT-RR relationship of isolated rat heart. Pharmacol Toxicol. 1992;70:402-6 pubmed
    ..We suggest that obidoxime modulates the direct effects of phosphamidon on the cardiac repolarization process. PD/OB at high concentrations invert the normal depolarization-repolarization coupling and may therefore potentiate arrhythmias...
  44. Krejcova G, Kassa J. Anticholinergic drugs--functional antidotes for the treatment of tabun intoxication. Acta Medica (Hradec Kralove). 2004;47:13-8 pubmed
    ..Antidotal treatment involving centrally acting anticholinergic drugs (benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine...
  45. Reiner E, Simeon Rudolf V. Pyridinium, imidazolium and quinuclidinium compounds: toxicity and antidotal effects against the nerve agents Tabun and Soman. Arh Hig Rada Toksikol. 2006;57:171-9 pubmed
  46. Eyer P, Radtke M, Worek F. Reactions of isodimethoate with human red cell acetylcholinesterase. Biochem Pharmacol. 2008;75:2045-53 pubmed publisher
    ..In fact, aging of AChE in dimethoate-poisoned patients on admission was much more advanced than expected from the reaction with omethoate. Manufacturers, researching scientists and clinical toxicologists should be aware of this problem...
  47. 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...
  48. dos Santos A, dos Santos D, Dafre A, de Bem A, Souza D, da Rocha J, et al. In vitro reactivating effects of standard and newly developed oximes on malaoxon-inhibited mouse brain acetylcholinesterase. Basic Clin Pharmacol Toxicol. 2010;107:768-73 pubmed publisher
  49. 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...
  50. 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...
  51. 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...
  52. Stenzel J, Worek F, Eyer P. Preparation and characterization of dialkylphosphoryl-obidoxime conjugates, potent anticholinesterase derivatives that are quickly hydrolyzed by human paraoxonase (PON1192Q). Biochem Pharmacol. 2007;74:1390-400 pubmed
    ..It is concluded that the pharmacogenetic PON1Q192R polymorphism may be another contributor to the large variability of susceptible subjects seen in obidoxime-treated patients...
  53. Schrickel J, Lewalter T, Luderitz B, Nickenig G, Klehr H, Rabe C. Recovery from ultra-high dose organophosphate poisoning after "in-the-field" antidote treatment: potential lessons for civil defense. J Emerg Med. 2009;37:279-82 pubmed publisher
    ..We believe that in cases of mass poisonings--for example, terrorist activity--therapy must be available on the scene as soon as possible. This also may require decentralized antidote storage...
  54. Worek F, Herkert N, Koller M, Aurbek N, Thiermann H. Interaction of pentylsarin analogues with human acetylcholinesterase: a kinetic study. Toxicol Lett. 2009;187:119-23 pubmed publisher
  55. Das Gupta S, Ghosh A, Chowdhri B, Asthana S, Batra B. Actions and interactions of cholinolytics and cholinesterase reactivators in the treatment of acute organophosphorus toxicity. Drug Chem Toxicol. 1991;14:283-91 pubmed
    ..I. of 3.2 when administered with HS-6, another bispyridinium ChE reactivator. This beneficial effect of benactyzine is possibly due to its greater antimuscarinic effect in the central nervous system than atropine or dexetimide...
  56. Luo C, Saxena A, Smith M, Garcia G, Radic Z, Taylor P, et al. Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium. Biochemistry. 1999;38:9937-47 pubmed
    ..Our results emphasize that certain oximes, such as LüH6 and TMB4, if used in the treatment of OP pesticide poisoning may cause prolonged inhibition of AChE due to formation of phosphoryl oximes...
  57. Redka D, Pisterzi L, Wells J. Binding of orthosteric ligands to the allosteric site of the M(2) muscarinic cholinergic receptor. Mol Pharmacol. 2008;74:834-43 pubmed publisher
    ..Ligands generally assumed to be exclusively orthosteric therefore can act at the allosteric site of the M(2) receptor, albeit at comparatively high concentrations...
  58. Thiermann H, Eyer F, Felgenhauer N, Pfab R, Zilker T, Eyer P, et al. Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds. Toxicol Lett. 2010;197:236-42 pubmed publisher
    ..An obidoxime plasma level in the range of 10-20 microM was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients...
  59. Worek F, Aurbek N, Wille T, Eyer P, Thiermann H. Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase. Toxicol Lett. 2011;200:19-23 pubmed publisher
  60. Kassa J, Bajgar J. [Comparison of the therapeutic effectiveness of selected cholinesterase reactivators with atropine in acute fosdrine poisoning in mice]. Ceska Slov Farm. 1996;45:31-4 pubmed
    ..In the therapy of intoxication 2 minutes after the exposure of experimental animals to fosdrine, the effect of the antidotal therapy was relatively low regardless of the selected oxime...
  61. Worek F, Diepold C, Eyer P. Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics. Arch Toxicol. 1999;73:7-14 pubmed
    ..Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status...
  62. Kassa J, Karasova J. A comparison of the potency of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) to counteract soman-induced neurotoxicity in rats. Drug Chem Toxicol. 2007;30:117-31 pubmed
    ..The oxime HI-6 is still the best acetylcholinesterase reactivator for the antidotal treatment of acute poisonings with soman...
  63. Pejchal J, Osterreicher J, Kuca K, Jun D, Bajgar J, Kassa J. The influence of acetylcholinesterase reactivators on selected hepatic functions in rats. Basic Clin Pharmacol Toxicol. 2008;103:119-23 pubmed publisher
    ..We found impaired hepatic transporter function after administration of HI-6, obidoxime and higher concentration of K027, which might be the underlying mechanism of acetylcholinesterase reactivators' hepatotoxicity...
  64. Nurulain S, Lorke D, Hasan M, Shafiullah M, Kuca K, Musilek K, et al. Efficacy of eight experimental bispyridinium oximes against paraoxon-induced mortality: comparison with the conventional oximes pralidoxime and obidoxime. Neurotox Res. 2009;16:60-7 pubmed publisher
    ..Further studies in other species exposed to a broader spectrum of OPCs are, however, necessary before considering their use in humans...
  65. Kassa J, Bielavský J. The efficacy of monopyridinium (2-PAAM, 2-PAEM) and bispyridinium (obidoxime, HI-6) oximes against mevinphos in mice. Pharmacol Toxicol. 1997;81:144-6 pubmed
  66. 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...
  67. Petroianu G, Nurulain S, Nagelkerke N, Shafiullah M, Kassa J, Kuca K. Five oximes (K-27, K-48, obidoxime, HI-6 and trimedoxime) in comparison with pralidoxime: survival in rats exposed to methyl-paraoxon. J Appl Toxicol. 2007;27:453-7 pubmed
  68. Lorke D, Nurulain S, Hasan M, Kuca K, Musilek K, Petroianu G. Eight new bispyridinium oximes in comparison with the conventional oximes pralidoxime and obidoxime: in vivo efficacy to protect from diisopropylfluorophosphate toxicity. J Appl Toxicol. 2008;28:920-8 pubmed publisher
    ..Dosage calculations based on in vitro IC50 measurements may therefore in future replace in vivo LD50 determinations, thereby reducing the number of animals required...
  69. Mercey G, Verdelet T, Saint André G, Gillon E, Wagner A, Baati R, et al. First efficient uncharged reactivators for the dephosphylation of poisoned human acetylcholinesterase. Chem Commun (Camb). 2011;47:5295-7 pubmed publisher
    ..Herein, we describe two first extremely promising uncharged reactivators for poisoned human AChE with a superior or similar in vitro ability to reactivate the enzyme as compared to that of HI-6, obidoxime, TMB-4 and HLö-7...
  70. Patocka J, Jakl A, Bajgar J, Fusek J. Efficacy of various pretreatment and therapy regimens against soman lethality in mice. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove. 1991;34:243-7 pubmed
    ..Combination of pyridostigmine with trihexyphenidyl, benactyzine and bis-(4-hydroxyiminomethyl) pyridinium-methane dichloride improved prophylactic action even further...
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    ..The clinical course of this patient did not support a cause-and-effect relationship between obidoxime and the abnormal liver function...
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    ..By using different oxime concentrations a combination of oxime doses may be suggested which could be an alternative to individual obidoxime or HI 6 autoinjectors...
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    ..In this article we report effects on neuromuscular function, oxime and atropine concentration, and relate them to acetylcholinesterase (AChE) activity...
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    ..The ability to depict these changes early and noninvasively may be applied clinically in the acute phase of organophosphate poisoning...
  75. Bartosova L, Kuca K, Kunesova G. Effectivity of new acetylcholinesterase reactivators in treatment of cyclosarin poisoning in mice and rats. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005;149:425-7 pubmed
    ..The BI-6 oxime was significantly more efficacious than obidoxime (in both mice and rats) and HS-6 (in rats) but its effectiveness did not reach the efficacy of HI-6...
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    ..3P-2 and 3P-3, respectively exhibited 80% and 69% regeneration of inhibited AChE, whereas 2-PAM (well known antidote for nerve agent poisoning) showed 42% regeneration...
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    ..The in vitro release study showed a sustained release profile, indicating the suitability of the developed formulation for the transport of oximes across the BBB...
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    ..e. the muscarinic receptor site and an allosteric effector site, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)..
  80. 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
  81. Aurbek N, Herkert N, Koller M, Thiermann H, Worek F. Kinetic analysis of interactions of different sarin and tabun analogues with human acetylcholinesterase and oximes: is there a structure-activity relationship?. Chem Biol Interact. 2010;187:215-9 pubmed publisher
    ..The recorded kinetic data did not allow a general statement concerning a structure-activity relationship between human AChE, OP and oximes...
  82. Kuca K, Musilek K, Pohanka M, Dohnal V, Patocka J. Reactivation potency of the acetylcholinesterase reactivator obidoxime is limited. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009;153:259-62 pubmed
    ..It is also needed by the fact that clinical findings considering this oxime are controversial...
  83. Soukup O, Krusek J, Kaniaková M, Kumar U, Oz M, Jun D, et al. Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors. Physiol Res. 2011;60:679-86 pubmed
    ..Taking together, the effects of tested oxime reactivators indicate an antagonism on both embryonic and adult form of the muscle nicotinic receptors...
  84. Kassa J, Karasova J, Tesarova S, Musilek K, Kuca K, Jung Y. A comparison of neuroprotective efficacy of the oxime K203 and its fluorinated analogue (KR-22836) with obidoxime in Tabun-poisoned rats. Basic Clin Pharmacol Toxicol. 2010;107:861-7 pubmed publisher
    ..Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime...
  85. Krishnan J, Arun P, Appu A, Vijayakumar N, Figueiredo T, Braga M, et al. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning. Neurotoxicology. 2016;53:64-73 pubmed publisher
    ..The addition of intranasally administered oximes to the current treatment regimen for organophosphate poisoning would improve efficacy, reducing both brain damage and mortality. ..
  86. Kassa J, Bajgar J. Therapeutic efficacy of obidoxime or HI-6 with atropine against intoxication with some nerve agents in mice. Acta Medica (Hradec Kralove). 1996;39:27-30 pubmed
    ..4 Higher doses of both oximes showed significantly more effective therapeutic efficacy against all nerve agents studied...
  87. Chen R, Raveh L, Zomber G, Rabinovitz I, Cohen G, Adani R, et al. Determination of therapeutic doses of bisquaternary oximes in large animals. J Appl Toxicol. 2001;21:285-91 pubmed
    ..The highest antidotal efficacy against tabun in dogs was obtained for toxogonin, whereas HLö-7 and AB-13 were most efficacious in monkeys...
  88. Kassa J, Karasova J, Vasina L. The evaluation of neuroprotective efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in cyclosarin-poisoned rats. J Appl Toxicol. 2007;27:621-30 pubmed
    ..Therefore, the oxime HI-6 is still the most suitable oxime for the antidotal treatment of acute poisonings with cyclosarin due to its neuroprotective as well as reactivating efficacy...
  89. 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
  90. Aurbek N, Thiermann H, Eyer F, Eyer P, Worek F. Suitability of human butyrylcholinesterase as therapeutic marker and pseudo catalytic scavenger in organophosphate poisoning: a kinetic analysis. Toxicology. 2009;259:133-9 pubmed publisher
    ..Furthermore, oxime-induced reactivation is too slow to accomplish a pseudo catalytic function, so that administered BChE may be merely effective as a stoichiometric scavenger...
  91. Zdarova Karasova J, Novotny L, Antos K, Zivna H, Kuca K. Time-dependent changes in concentration of two clinically used acetylcholinesterase reactivators (HI-6 and obidoxime) in rat plasma determined by HPLC techniques after in vivo administration. Anal Sci. 2010;26:63-7 pubmed
    ..62 +/- 3.563 microg/mL was recorded at about 10 min. HPLC with UV detection presented in our study is a general method which could be applied for quick measurements of bisquaternary AChE reactivators in rat plasma...
  92. Kufleitner J, Wagner S, Worek F, von Briesen H, Kreuter J. Adsorption of obidoxime onto human serum albumin nanoparticles: drug loading, particle size and drug release. J Microencapsul. 2010;27:506-13 pubmed publisher
    ..The in vitro release of obidoxime from HSA nanoparticles showed a rapid release of the drug from the nanoparticles within 3 h...