Genomes and Genes
Summary: Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates.
- Matos K, da Cunha E, da Silva Gonçalves A, Wilter A, Kuca K, França T, et al. First principles calculations of thermodynamics and kinetic parameters and molecular dynamics simulations of acetylcholinesterase reactivators: can mouse data provide new insights into humans?. J Biomol Struct Dyn. 2012;30:546-58 pubmed publisher
- Eddleston M, Eyer P, Worek F, Mohamed F, Senarathna L, von Meyer L, et al. Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005;366:1452-9 pubmed..We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause...
- 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
- Pang Y, Kollmeyer T, Hong F, Lee J, Hammond P, Haugabouk S, et al. Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003;10:491-502 pubmed..This type of binding may induce a conformational change in the acyl pocket loop which modulates the catalytic site via a domino effect. ..
- Musilek K, Holas O, Jun D, Dohnal V, Gunn Moore F, Opletalova V, et al. Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker: preparation and reactivation of tabun- and paraoxon-inhibited acetylcholinesterase. Bioorg Med Chem. 2007;15:6733-41 pubmed..However, extensive differences were found by a SAR study for various substitutions on the non-oxime part of the reactivator molecule. ..
- 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...
- Bartosova L, Kuca K, Kunesova G, Jun D. The acute toxicity of acetylcholinesterase reactivators in mice in relation to their structure. Neurotox Res. 2006;9:291-6 pubmed..All these structural features play an important role in biological activity of these compounds performed by their acute toxicity as well as by their reactivation potency. ..
- 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. ..
- Skovira J, O Donnell J, Koplovitz I, Kan R, McDonough J, Shih T. Reactivation of brain acetylcholinesterase by monoisonitrosoacetone increases the therapeutic efficacy against nerve agents in guinea pigs. Chem Biol Interact. 2010;187:318-24 pubmed publisher..These data show that MINA is capable of reactivating nerve agent-inhibited ChE and that the extent of ChE reactivation within the CNS strongly relates to its therapeutic efficacy. ..
- Pawar K, Bhoite R, Pillay C, Chavan S, Malshikare D, Garad S. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. 2006;368:2136-41 pubmed..We aimed to assess the effectiveness of a constant pralidoxime infusion compared with repeated bolus doses to treat patients with moderately severe poisoning from organophosphorus pesticides...
- Jokanovic M, Prostran M. Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Curr Med Chem. 2009;16:2177-88 pubmed..In this article, we review data on structure-activity relationship of pyridinium oximes and discuss their pharmacological and toxicological significance. ..
- Bajgar J, Fusek J, Kuca K, Bartosova L, Jun D. Treatment of organophosphate intoxication using cholinesterase reactivators: facts and fiction. Mini Rev Med Chem. 2007;7:461-6 pubmed..Basic part of the current standard treatment of organophosphate (OP) agent poisoning is administration of cholinesterase reactivators. It includes different types of oximes with a similar basic structure differing by the number of ..
- Kwong T. Organophosphate pesticides: biochemistry and clinical toxicology. Ther Drug Monit. 2002;24:144-9 pubmed..Patients who receive treatment promptly usually recover from acute toxicity but may suffer from neurologic sequelae. ..
- Marrs T, Rice P, Vale J. The role of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev. 2006;25:297-323 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. ..
- Odzak R, Calić M, Hrenar T, Primozic I, Kovarik Z. Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase. Toxicology. 2007;233:85-96 pubmed
- 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. ..
- 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...
- Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev. 2003;22:165-90 pubmed
- Kassa J, Kuca K, Karasova J, Musilek K. The development of new oximes and the evaluation of their reactivating, therapeutic and neuroprotective efficacy against tabun. Mini Rev Med Chem. 2008;8:1134-43 pubmed..Due to their therapeutic, reactivating and neuroprotective efficacy, all newly synthesized oximes appear to be suitable oximes for the antidotal treatment of acute tabun poisonings. ..
- Luo C, Leader H, Radic Z, Maxwell D, Taylor P, Doctor B, et al. Two possible orientations of the HI-6 molecule in the reactivation of organophosphate-inhibited acetylcholinesterase. Biochem Pharmacol. 2003;66:387-92 pubmed..These conclusions were further corroborated by reactivation studies using an analog of HI-6 in which the bispyridinium moieties are linked by a methylene bridge rather than an ether oxygen. ..
- Kovarik Z, Radic Z, Berman H, Simeon Rudolf V, Reiner E, Taylor P. Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugates. Biochemistry. 2004;43:3222-9 pubmed..Rates of reactivation reach values sufficient for consideration of mixtures of a mutant enzyme and an oxime as a scavenging strategy in protection and treatment of organophosphate exposure. ..
- 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
- Grosfeld H, Barak D, Ordentlich A, Velan B, Shafferman A. Interactions of oxime reactivators with diethylphosphoryl adducts of human acetylcholinesterase and its mutant derivatives. Mol Pharmacol. 1996;50:639-49 pubmed
- Bloch Shilderman E, Levy A. Transient and reversible nephrotoxicity of sarin in rats. J Appl Toxicol. 2007;27:189-94 pubmed..However, if renal impairments are left unattended, they might contribute to the overall toxic manifestation and as a result aggravate the clinical state of intoxicated casualties...
- Petroianu G, Arafat K, Nurulain S, Kuca K, Kassa J. In vitro oxime reactivation of red blood cell acetylcholinesterase inhibited by methyl-paraoxon. J Appl Toxicol. 2007;27:168-75 pubmedOximes are cholinesterase reactivators of use in poisoning with organophosphorus ester enzyme inhibitors. Pralidoxime (PRX) is the oxime used in the United States...
- 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
- Meggs W. Permanent paralysis at sites of dermal exposure to chlorpyrifos. J Toxicol Clin Toxicol. 2003;41:883-6 pubmed..Dermal exposure of the hands and feet to chlorpyrifos was associated with atrophy and permanent paralysis of exposed areas. The importance of protective equipment is emphasized. ..
- Petroianu G, Nurulain S, Nagelkerke N, Al Sultan M, Kuca K, Kassa J. Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime: survival in rats exposed to the organophosphate paraoxon. J Appl Toxicol. 2006;26:262-8 pubmedOximes are cholinesterase reactivators used in organophosphorus poisoning. Clinical experience with pralidoxime (PRX) and other oximes is disappointing and their routine use has been questioned...
- 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, 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. ..
- Benko B, Kalasz H, Ludanyi K, Petroianu G, Kuca K, Darvas F, et al. In vitro and in vivo metabolisms of K-48. Anal Bioanal Chem. 2007;389:1243-7 pubmed..The presence of unchanged K-48 in the serum and cerebrospinal fluid facilitates quantitative determination using HPLC separation and ultraviolet absorbance detection. ..
- McManus M. Neuromuscular blockers in surgery and intensive care, Part 2. Am J Health Syst Pharm. 2001;58:2381-95 pubmed..An understanding of the pharmacology, pharmacodynamics, and pharmacokinetics of NMBs will help health care providers gain expertise in the selection and use of these agents. ..
- 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...
- Bawaskar H, Joshi S. Organophosphorus poisoning in agricultural India--status in 2005. J Assoc Physicians India. 2005;53:422-4 pubmed
- Soukup O, Kristofikova Z, Proska J, Tobin G, Patocka J, Marek J, et al. Novel acetylcholinesterase reactivator K112 and its cholinergic properties. Biomed Pharmacother. 2010;64:541-5 pubmed publisher..All these cholinergic properties could significantly contribute to the antidotal effect of K112 at the poisoning by the organophosphates. ..
- Vioque Fernández A, de Almeida E, Ballesteros J, García Barrera T, Gomez Ariza J, Lopez Barea J. Doñana National Park survey using crayfish (Procambarus clarkii) as bioindicator: esterase inhibition and pollutant levels. Toxicol Lett. 2007;168:260-8 pubmed..However, no correlation exist between the pesticide concentration at different sites and the extent of esterase inhibition, indicating that other factors could affect esterase response of animals from polluted sites. ..
- Petroianu G, Ewald V, Thyes C, Missler A, Maleck W. Intravenous pyruvic acid application in minipigs partially protects acetylcholine-esteratic but not butyrylcholine-esteratic activity in plasma from inhibition by paraoxon. J Appl Toxicol. 2003;23:37-42 pubmed..Also, a combination therapy with l-lactate and pyruvic acid in vivo should be investigated. ..
- Wagner S, Kufleitner J, Zensi A, Dadparvar M, Wien S, Bungert J, et al. Nanoparticulate transport of oximes over an in vitro blood-brain barrier model. PLoS ONE. 2010;5:e14213 pubmed publisher..This is very important for survival after severe OP intoxication. Therefore, these nanoparticulate formulations are promising formulations for the treatment of the peripheral and the CNS after OP poisoning. ..
- Fujino Y, Inoue Y, Onodera M, Endo K, Endo S, Nakayama H, et al. [Three cases of organophosphate poisoning treated with pralidoxime iodide and whole-bowel irrigation]. Chudoku Kenkyu. 2004;17:273-7 pubmed..Serum ChE improved within two days. These cases suggest the possibility that preferential whole-bowel irrigation without atropine sulfate prevents the persistence or recurrence of the toxic effects of organophosphate. ..
- Sakurada K, Ikegaya H, Ohta H, Fukushima H, Akutsu T, Watanabe K. Effects of oximes on mitochondrial oxidase activity. Toxicol Lett. 2009;189:110-4 pubmed publisher..This hypothesis should be further investigated by in vivo study, including kinetic determination and free radical work. ..
- Fernandez Cabezudo M, Lorke D, Azimullah S, Mechkarska M, Hasan M, Petroianu G, et al. Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium. Immunology. 2010;130:388-98 pubmed publisher..Hence, in a model of Gram-negative bacterial infection, cholinergic stimulation is shown to enhance the anti-microbial immune response leading to effective control of bacterial proliferation and enhanced animal survival. ..
- Shih T, Skovira J, O Donnell J, McDonough J. Evaluation of nine oximes on in vivo reactivation of blood, brain, and tissue cholinesterase activity inhibited by organophosphorus nerve agents at lethal dose. Toxicol Mech Methods. 2009;19:386-400 pubmed publisher..Overall, MMB-4 appeared to be, among all oximes tested, the most effective in vivo AChE reactivator against the broadest spectrum of nerve agents. ..
- Herkert N, Freude G, Kunz U, Thiermann H, Worek F. Comparative kinetics of organophosphates and oximes with erythrocyte, muscle and brain acetylcholinesterase. Toxicol Lett. 2012;209:173-8 pubmed publisher..These data support the view that AChE from different tissue has similar kinetic properties and that brain AChE is comparably susceptible toward reactivation by oximes. ..
- Zabrodskii P, Kirichuk V, Romashchenko S, Germanchuk V. [Effect of the cholinesterase reactivator dipyroxime in various models of delayed hypersensitivity during acute intoxication by acrylonitrile]. Eksp Klin Farmakol. 2000;63:47-9 pubmed..Dipiroxime partly recovered DTH in various experimental series (except for the reaction of suppressor cell transfer) by restoring the alpha-naphthylbutyratesterase activity in cells of the lymphoid organs studied...
- Kassa J, Musilek K, Karasova J, Kuca K, Bajgar J. Two possibilities how to increase the efficacy of antidotal treatment of nerve agent poisonings. Mini Rev Med Chem. 2012;12:24-34 pubmed
- Gaso Sokac D, Katalinić M, Kovarik Z, Busić V, Kovac S. Synthesis and evaluation of novel analogues of vitamin B6 as reactivators of tabun and paraoxon inhibited acetylcholinesterase. Chem Biol Interact. 2010;187:234-7 pubmed publisher..The maximum restored enzyme activity in 24h was below 25%. Therefore, this class of compounds cannot be considered as potential improvement in a search for new and more efficient antidotes against OP poisoning. ..
- Küçükkilinç T, Cochran R, Kalisiak J, Garcia E, Valle A, Amitai G, et al. Investigating the structural influence of surface mutations on acetylcholinesterase inhibition by organophosphorus compounds and oxime reactivation. Chem Biol Interact. 2010;187:238-40 pubmed publisher..These results indicate that selected residues outside the active center influence inhibition, reactivation and catalysis rates through longer range interactions. ..
- Wei Z, Liu Y, Wang S, Yao L, Nie H, Wang Y, et al. Conjugates of salicylaldoximes and peripheral site ligands: Novel efficient nonquaternary reactivators for nerve agent-inhibited acetylcholinesterase. Bioorg Med Chem. 2017;25:4497-4505 pubmed publisher..Moreover, due to greatly improved lipophilicity, these nonquaternary conjugates hold promise for the development of efficient centrally activating reactivators. ..
- 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. ..
- Eyer P, Szinicz L, Thiermann H, Worek F, Zilker T. Testing of antidotes for organophosphorus compounds: experimental procedures and clinical reality. Toxicology. 2007;233:108-19 pubmed..The experience gathered with the experimental and therapeutic approaches to human poisoning by OP pesticides may be helpful when oximes have to be selected against nerve agents. ..
- Eyer P, Buckley N. Pralidoxime for organophosphate poisoning. Lancet. 2006;368:2110-1 pubmed
- Buncel E, Cannes C, Chatrousse A, Terrier F. Reactions of oximate alpha-nucleophiles with esters: evidence from solvation effects for substantial decoupling of desolvation and bond formation. J Am Chem Soc. 2002;124:8766-7 pubmed..This is interpreted as due to virtually complete decoupling between desolvation of the oxyanion nucleophile and bond formation in the rate-determining transition state (solvational imbalance). ..
- Read R, Riches J, Stevens J, Stubbs S, Black R. Biomarkers of organophosphorus nerve agent exposure: comparison of phosphylated butyrylcholinesterase and phosphylated albumin after oxime therapy. Arch Toxicol. 2010;84:25-36 pubmed publisher..No BuChE adducts were detected in animals exposed to sarin and cyclosarin where samples were collected only after 23 or 24 days. ..
- Lo R, Chandar N, Ghosh S, Ganguly B. The reactivation of tabun-inhibited mutant AChE with Ortho-7: steered molecular dynamics and quantum chemical studies. Mol Biosyst. 2016;12:1224-31 pubmed publisher..0 kcal mol(-1)). The study reveals that both the orientation of the oxime reactivator for nucleophilic attack and the stabilization of the reactivator at the active site would be crucial for the design of an efficient reactivator. ..
- Kuca K, Kassa J. A comparison of the ability of a new bispyridinium oxime--1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane dibromide and currently used oximes to reactivate nerve agent-inhibited rat brain acetylcholinesterase by in vitro methods. J Enzyme Inhib Med Chem. 2003;18:529-35 pubmed
- Guarisco J, O Donnell J, Skovira J, McDonough J, Shih T. In vivo oxime administration does not influence Ellman acetylcholinesterase assay results. Toxicol Mech Methods. 2009;19:379-85 pubmed publisher..Inclusion of an oxime control group to insure that this particular type of interference is not causing false readings in the assay is a prudent step. ..
- 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...
- Gyenge M, Kalasz H, Petroianu G, Laufer R, Kuca K, Tekes K. Measurement of K-27, an oxime-type cholinesterase reactivator by high-performance liquid chromatography with electrochemical detection from different biological samples. J Chromatogr A. 2007;1161:146-51 pubmed..The method--with slight modification in the composition of the mobile phase--can be used to measure a wide range of other related pyridinium aldoxime-type cholinesterase reactivators.
- Taysse L, Daulon S, Delamanche S, Bellier B, Breton P. Skin decontamination of mustards and organophosphates: comparative efficiency of RSDL and Fuller's earth in domestic swine. Hum Exp Toxicol. 2007;26:135-41 pubmed..Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin. ..
- Karalliedde L, Baker D, Marrs T. Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy. Toxicol Rev. 2006;25:1-14 pubmed..This has led to speculation that myopathy is involved in the causation of the IMS. However, while myopathy and the IMS have a common origin in acetylcholine accumulation, they are not causally related to one another. ..
- 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 18.104.22.168). AChE reactivators (also known as oximes) are generally used for the reactivation of an inhibited enzyme...
- Voicu V, Albu F, Tache F, Musilek K, Kuca K, Medvedovici A. LC-MS/MS approaches for the assay of bis-quaternary pyridinium oximes used as AChE reactivators in biological matrices. Bioanalysis. 2013;5:793-809 pubmed publisher..LLOQ in the tenths of nanogram per milliliter range are achievable. ..
- 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. ..
- Yanagisawa N, Morita H, Nakajima T. Sarin experiences in Japan: acute toxicity and long-term effects. J Neurol Sci. 2006;249:76-85 pubmed..In summary, both potent toxicity and quick recovery from critical ill conditions were prominent features. Conventional therapies proved effective in Sarin incidents in Japan. ..
- Simkhada N, Kafle K, Prasad P. Pralidoxime in organophosphorus poisoning. JNMA J Nepal Med Assoc. 2010;50:300-2 pubmed..The initial dose of Pralidoxime used was 1 gm followed by maintenance dose of 500mg 6 hourly, the doses prescribed were less than WHO recommended doses. ..
- Barelli A, Soave P, Del Vicario M, Barelli R. New experimental Oximes in the management of organophosphorus pesticides poisoning. Minerva Anestesiol. 2011;77:1197-203 pubmed
- Aurbek N, Thiermann H, Szinicz L, Eyer P, Worek F. Application of kinetic-based computer modelling to evaluate the efficacy of HI 6 in percutaneous VX poisoning. Toxicology. 2006;224:74-80 pubmed..Hence, designing animal experiments with the aid of computer modeling may reduce the number of animal experiments and allow a more reliable extrapolation of animal data to humans. ..
- Kuca K, Dohnal V. 1,3-Bis(2-hydroxyiminomethylpyridinium) propane as the potential reactivator of the acetylcholinesterase inhibited by nerve agents. Acta Medica (Hradec Kralove). 2004;47:167-9 pubmed..The maximum concentration of pralidoxime was reached at the concentrations 10(-1) M (for cyclosarin) and 10(-3) M (for VX) but these concentrations are not available for the use in vivo. ..
- Bawaskar H, Joshi S. High-dose pralidoxime for organophosphorus poisoning. Lancet. 2007;369:1425; author reply 1427 pubmed
- Kovarik Z, Radic Z, Berman H, Taylor P. Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonates. Toxicology. 2007;233:79-84 pubmed..Our results confirm that a mixture of a mutant enzyme and an oxime might serve as an in vivo catalytic scavenger of organophosphates. ..
- Worek F, Aurbek N, Thiermann H. Reactivation of organophosphate-inhibited human AChE by combinations of obidoxime and HI 6 in vitro. J Appl Toxicol. 2007;27:582-8 pubmed..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...