Acta Med. 2021, 64: 145-152

https://doi.org/10.14712/18059694.2021.25

A Comparison of the Neuroprotective and Reactivating Efficacy of a Novel Bispyridinium Oxime K870 with Commonly Used Pralidoxime and the Oxime HI-6 in Tabun-Poisoned Rats

Jiří Kassaa,*, Jana Hatlapatkováa, Jana Žďárová Karasováa, Vendula Hepnarováa, Filip Caisbergerb, Jaroslav Pejchala

aDepartment of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Hradec Králové, Czech Republic
bNeurology, University Hospital Hradec Králové, Hradec Králové, Czech Republic

Received March 16, 2021
Accepted June 16, 2021

References

1. Black R. Development, historical use and properties of chemical warfare agents. In: Worek F, Jenner J, Thierman H, eds. Chemical Warfare Toxicology, Royal Society of Chemistry, Cambridge, 2016: 1–28.
2. Bajgar J. Organophosphate/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 2004; 38: 151–216. <https://doi.org/10.1016/S0065-2423(04)38006-6>
3. Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 2013; 11: 315–35. <https://doi.org/10.2174/1570159X11311030006> <PubMed>
4. Delfino RT, Ribeiro TS, Figueroa-Villar JD. Organophosphorus compounds as chemical warfare agents: a review. J Braz Chem Soc 2009; 20: 407–28. <https://doi.org/10.1590/S0103-50532009000300003>
5. Cabal J, Bajgar J. Tabun – reappearance 50 years later (in Czech). Chem Listy 1999; 93: 27–31.
6. Ekström F, Akfur C, Tunemalm AK, 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. <https://doi.org/10.1021/bi051286t>
7. Hoffman A, Eisenkraft A, Finkelstein A, Schein O, Rotman E, Dushnitsky T. A decade after the Tokyo sarin attack: a review of neurological follow-up of the victims. Mil Med 2007; 172: 607–10. <https://doi.org/10.7205/MILMED.172.6.607>
8. Yamasue H, Abe O, Kasai K, et al. Human brain structural changes related to acute single exposure to sarin. Ann Neuro 2007; 61: 37–46. <https://doi.org/10.1002/ana.21024>
9. 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. <https://doi.org/10.2174/092986709788612729>
10. Marrs TC, Rice P, Vale JA. The role of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev 2006; 25: 297–323. <https://doi.org/10.2165/00139709-200625040-00009>
11. Wilhelm CM, Snider TH, Babin MC, Jett DA, Platoff GEJr, Yeung DT. A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides. Toxicol Appl Pharmacol 2014; 281: 254–65. <https://doi.org/10.1016/j.taap.2014.10.009> <PubMed>
12. Zorbaz T, Malinak D, Marakovic N, et al. Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physicochemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents. J Med Chem 2018; 61: 10753–66. <https://doi.org/10.1021/acs.jmedchem.8b01398>
13. Jun D, Kuca K, Stodulka P, et al. HPLC analysis of HI-6 dichloride and dimethanesulfonate – antidotes against nerve agents and organophosphorus pesticides. Anal Lett 2007; 40: 2783–7. <https://doi.org/10.1080/00032710701588531>
14. Kassa J, Misik J, Hatlapatkova J et al. The evaluation of the reactivating nad neuroprotective efficacy of two newly prepared bispyridinium oximes (K305, K307) in tabun-poisoned rats – a comparison with trimedoxime and the oxime K203. Molecules 2017; 22: 1152. <https://doi.org/10.3390/molecules22071152> <PubMed>
15. Moser VC, Tilson H, McPhail RC et al. The IPCS collaborative study on neurobehavioral screening methods: II. Protocol design and testing procedures. NeuroToxicology 1997; 18: 929–38.
16. Ellman GL, Courtney DK, Andres VJr, Feartherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88–93. <https://doi.org/10.1016/0006-2952(61)90145-9>
17. Clement JG, Hansen AS, Boulet CA. Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice. Arch Toxicol 1992; 66: 216–9. <https://doi.org/10.1007/BF01974018>
18. Paxinos G, Watson C. The rat brain in stereotactic coordinates, 6th ed. Academic Press, San Diego, 2006: 307.
19. Chen Y. Organophosphate-induced brain damage: Mechanisms, neuropsychiatric and neurological consequences, and potential therapeutic strategies. NeuroToxicology 2012; 33: 391–400. <https://doi.org/10.1016/j.neuro.2012.03.011>
20. Shih TM, Duniho SM, McDonough JH. Control of NA-induced seizures is critical for neuroprotection and survival. Toxicol Appl Pharmacol 2003; 188: 69–80. <https://doi.org/10.1016/S0041-008X(03)00019-X>
21. Kassa J, Kunesova G. Comparison of the neuroprotective effects of the newly developed oximes (K027, K048) with trimedoxime in tabun-poisoned rats. J Appl Biomed 2006; 4: 123–34. <https://doi.org/10.32725/jab.2006.013>
22. McDonough JHJr, Zoeffel LD, McMonagle J, Copeland TL, Smith CD, Shih TM. Anticonvulsant treatment of nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea-pigs. Epilepsy Res 2000; 38: 1–14. <https://doi.org/10.1016/S0920-1211(99)00060-1>
23. Jokanovic M. Structure-activity relationship and efficacy of pyridinium oximes in the treatment of poisoning with organophosphorus compounds: a review of recent data. Curr Topic Med Chem 2012; 12: 1775–89. <https://doi.org/10.2174/1568026611209061775>
24. Kassa J, Krejcova G. Neuroprotective effects of currently used antidotes in tabun-poisoned rats. Pharmacol Toxicol 2003; 92: 258–64. <https://doi.org/10.1034/j.1600-0773.2003.920602.x>
25. Worek F, Widmann R, Knopff O, Szinicz L. Reactivating potency of obidoxime, pralidoxime, HI-6 and HLö-7 in human erythrocyte acetylcholinesterase inhibited by highly toxic organophosphorus compounds. Arch Toxicol 1998; 72: 237–43. <https://doi.org/10.1007/s002040050495>
26. Zdarova Karasova J, Pohanka M, Musilek K, Zemek F, Kuca K. Passive diffusion of acetylcholinesterase oxime reactivators through the blood-brain barrier: Influence of molecular structure. Toxicol in Vitro 2010; 24: 1838–44.
27. de Koning MC, van Grol M, Noort D. Peripheral site ligand conjugation to a non quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase. Toxicol Lett 2011; 206: 54–9. <https://doi.org/10.1016/j.toxlet.2011.04.004>
28. Masson P, Nachon F, Lockridge O. Structural approach to the aging of phosphylated cholinesterases. Chem Biol Interact 2010; 187: 157–62. <https://doi.org/10.1016/j.cbi.2010.03.027>
29. Kuca K, Jun D, Musilek K. Structural requirements of acetylcholinesterase reactivators. Mini Rev Med Chem 2006; 6: 269–77. <https://doi.org/10.2174/138955706776073510>
30. Musilek K, Kuca K, Jun D, Dolezal M. Progress in synthesis of new acetylcholinesterase reactivators during the period 1990–2004. Curr Org Chem 2007; 11: 229–38. <https://doi.org/10.2174/138527207779316417>
31. Niessen KV, Tattersall JEH, Timperley CM, et al. Interaction of bispyridinium compounds with the orthosteric binding site of human α7 and Torpedo californica nicotinic acetylcholine receptors (nAChRs). Toxicol Lett 2011; 206: 100–4. <https://doi.org/10.1016/j.toxlet.2011.06.009>
32. Sürig U, Gaal K, Kostenis E, Tränkle C, Mohr K, Holzgrabe U. Muscarinic allosteric modulators. Atypical structure-activity-relationships in bispyridinium-type compounds. Arch Pharm Chem Life Sci 2006; 339: 207–12. <https://doi.org/10.1002/ardp.200600005>
33. Van Helden HPM, Busker RW, Melchers BPC, Bruijnzeel PLB. Pharmacological effects of oximes: how relevant are they? Arch Toxicol 1996; 70: 779–86. <https://doi.org/10.1007/s002040050340>
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