JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2010, 59(1):18-22

Evaluation of the reactivating efficacy of selected reactivators of paraoxon-inhibited acetylcholinesterase in vitro

O. Holas1, K. Musílek1,2,*, V. Opletalová1, K. Kuča2,3
1 Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, Katedra farmaceutické chemie a kontroly léčiv
2 Univerzita obrany Brno, Fakulta vojenského zdravotnictví Hradec Králové, Katedra toxikologie
3 Univerzita obrany Brno, Fakulta vojenského zdravotnictví Hradec Králové, Centrum pokročilých studií

Organophosphorus pesticides (OPs) are ranked among the group of highly toxic irreversible inhibitors of acetylcholinesterase (AChE). The causal drugs in OPs intoxications are oxime reactivators of AChE. The reactivating efficacy of five newly prepared bispyridinium reactivators of acetylcholinesterase was tested on a model of a paraoxon-inhibited enzyme. The reactivating efficacy was tested by means of the standard in vitro test, the laboratory rat brain homogenate being used as the source of acetylcholinesterase. The result were compared with five commercially available AChE reactivators.

Keywords: acetylcholinesterase; organophosphorus pesticide; reactivator; in vitro; SAR

Received: November 15, 2009; Accepted: January 4, 2010; Published: January 1, 2010  Show citation

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Holas O, Musílek K, Opletalová V, Kuča K. Evaluation of the reactivating efficacy of selected reactivators of paraoxon-inhibited acetylcholinesterase in vitro. Čes. slov. farm. 2010;59(1):18-22.
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    References

    1. Bajgar, J.: Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv. Clin. Chem., 2004; 38, 151-216. Go to original source... Go to PubMed...
    2. Marrs, T. C.: Organophosphate poisoning. Pharmacol. Therapeut., 1993; 58, 51-66. Go to original source... Go to PubMed...
    3. Patocka, J., Kuca, K., Jun D.: Acetylcholinesterase and butyrylcholinesterase - important enzymes of human body. Acta Medica, 2004; 47, 215-228. Go to original source...
    4. Satoh, T., Hosokawa, M.: Organophosphates and their impact on the global environment. Neurotoxicol., 2000; 21, 223-227.
    5. Francotte, P., Graindorge, E., Boverie, S., de Tullio, P., Pirotte B.: Curr. Med. Chem., 2004; 11, 1757-1778. Go to original source... Go to PubMed...
    6. Marklund, A., Andersson, B., Haglund, P.: Organophosphorus flame retardants and plasticizers in air from various indoor environments. J. Environ. Monit., 2005; 7, 814-819. Go to original source... Go to PubMed...
    7. Tattersall, J.: Seizure activity post organophosphate exposure. Front. Biosci., 2009; 14, 3688-3711. Go to original source... Go to PubMed...
    8. Patocka, J.: Vojenská toxikologie. 1. vyd. Praha: Grada Publishing a.s., 2004; 180.
    9. 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, 461-466. Go to original source... Go to PubMed...
    10. Newmark, J.: Nerve agents. Neurologist, 2007; 13, 20-32. Go to original source... Go to PubMed...
    11. Saxena, A., Sun, W., Luo, C., Myers, T. M., Koplovitz, I., Lenz, D. E., Doctor, B. P.: Bioscavenger for protection from toxicity of organophosphorus compounds. J. Mol. Neurosci., 2006; 30, 145-148. Go to original source... Go to PubMed...
    12. Kuca, K., Jun, D., Musilek, K.: Structural requirements of acetylcholinesterase reactivators. Mini-Rev. Med. Chem., 2006; 3, 269-277. Go to original source... Go to PubMed...
    13. Poziomek, E. J., Hackley, B. E., Steinberg, G. M.: Pyridinium aldoximes. J. Org. Chem., 1958; 23, 714-717. Go to original source...
    14. Kuca, K., Jun, D., Musilek, K. Bajgar, J.: Reactivators of tabun-inhibited acetylcholinesterase: Structure-biological activity relationship. Front. Drug. Des. Discov., 2007; 3, 381-394. Go to original source...
    15. Ekstrom, F., Pang, Y. P., Boman, M., Artursson, E., Akfur, C., Borjegren, S.: Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime: structural basis for differences in the ability to reactivate tabun conjugates. Biochem. Pharmacol., 2006; 72, 597-607. Go to original source... Go to PubMed...
    16. Ekstrom, F., Akfur, C., Tunemalm, A. K., Lundberg, S.: Structural changes of phenylalanine 338 and histidine 447 revealed by the crystal structures of tabun-inhibited murine acetylcholinesterase. Biochemistry, 2006; 45, 74-81. Go to original source... Go to PubMed...
    17. Eddelston, M., Dawson, A. H., Buckley, N. A.: Management of acute organophosphorus pesticide poisoning. Lancet, 2008; 371, 597-607. Go to original source... Go to PubMed...
    18. Tattersall, J. E.: Ion channel blockade by oximes and recovery of diaphragm muscle from soman poisoning in vitro. Br. J. Pharmacol., 1993; 108, 1006-1015. Go to original source... Go to PubMed...
    19. Kuca, K., Cabal, J., Musilek, K., Jun, D., Bajgar, J.: Effective bisquaternary reactivators of tabun-inhibited AChE. J. Appl. Toxicol., 2005; 25, 491-495. Go to original source... Go to PubMed...
    20. Musilek, K., Holas, O., Kuca, K., Jun, D., Dohnal, V., Dolezal, M.: Synthesis of asymmetrical bispyridinium compounds bearing cyano-moiety and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. Bioorg. Med. Chem. Lett., 2006; 16, 5673-5676. Go to original source... Go to PubMed...
    21. 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, 291-296. Go to original source... Go to PubMed...
    22. Worek, F., Thiermann, H., Szinicz, L., Eyer, P.: Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes. Biochem. Pharmacol., 2004; 68, 2237-2248. Go to original source... Go to PubMed...
    23. Racakova, V., Jun, D., Opletalova, V., Kuca, K.: Reactivation of acetycholinesterase inhibited by the pesticide chlorpyrifos. J. Appl. Biomed., 2006; 4, 147-151. Go to original source...
    24. Musilek, K., Holas, O., Kuca, K., Jun, D., Dohnal, V., Opletalova, V., Dolezal, M.: 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, 3172-3176. Go to original source... Go to PubMed...
    25. Sakurada, K., Matsubara, K., Shimizu, K., Shiono, H., Seto, Y., Tsuge, K., Yoshino, M., Sakai, I., Mukoyama, H., Takatori, T.: Pralidoxime iodide (2-pAM) penetrates across the blood-brain barrier. Neurochem. Res., 2003; 28, 1401-1407. Go to original source... Go to PubMed...
    26. Okuno, S., Sakurada, K., Ohta, H., Ikegaya, H., Kazui, Y., Akutsu, T., Takatori, T., Iwadate, K.: Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS. Toxicol. Appl. Pharmacol., 2008; 227, 8-15. Go to original source... Go to PubMed...
    27. Lorke, D. E., Hasan, M. Y., Nurulain, S. M., Sheen, R., Kuca, K., Petroianu, G. A.: Entry of two new asymmetric bispyridinium oximes (K-27 and K-48) into the rat brain: comparison with obidoxime. J. Appl. Toxicol., 2007; 27, 482-490. Go to original source... Go to PubMed...
    28. Kuca, K., Patocka, J.: Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium-oximes. J. Enzym. Inhib. Med. Chem., 2004; 19, 19-22. Go to original source... Go to PubMed...
    29. Musilek, K., Holas, O., Kuca K., Jun D., Dohnal, V., Opletalova, 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. Enzym. Inhib. Med. Chem., 2007; 22, 425-432. Go to original source... Go to PubMed...

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