The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats-A Comparison with Trimedoxime and the Oxime K203

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2017 Jul 12

PMID 28696367

Citations 3

Authors

Jiri Kassa

Jan Misik

Jana Hatlapatkova

Jana Zdarova Karasova

Vendula Sepsova

Filip Caisberger

Jaroslav Pejchal

Affiliations

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Abstract

The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime while the ability of the oxime K307 to reactivate tabun-inhibited acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In addition, only one newly developed oxime (K307) combined with atropine was able to markedly decrease tabun-induced neurotoxicity although it did not eliminate all tabun-induced acute neurotoxic signs and symptoms. These results correspond to the histopathological evaluation of tabun-induced brain damage. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime) in the treatment of acute tabun poisonings.

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References

Lorke D, Kalasz H, Petroianu G, Tekes K . Entry of oximes into the brain: a review. Curr Med Chem. 2008; 15(8):743-53. DOI: 10.2174/092986708783955563. View

Bajgar J . Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem. 2004; 38:151-216. DOI: 10.1016/s0065-2423(04)38006-6. View

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(6):1838-44. DOI: 10.1016/j.tiv.2010.05.009. View

Kassa J, Karasova J, Vasina L, Bajgar J, Kuca K, Musilek K . A comparison of neuroprotective efficacy of newly developed oximes (K203, K206) and commonly used oximes (obidoxime, HI-6) in tabun-poisoned rats. Drug Chem Toxicol. 2009; 32(2):128-38. DOI: 10.1080/01480540802593873. View

Clement J, Hansen A, Boulet C . Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice. Arch Toxicol. 1992; 66(3):216-9. DOI: 10.1007/BF01974018. View

McDonough Jr J, Zoeffel L, McMonagle J, Copeland T, Smith C, Shih T . Anticonvulsant treatment of nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea pigs. Epilepsy Res. 1999; 38(1):1-14. DOI: 10.1016/s0920-1211(99)00060-1. View

Antonijevic B, Stojiljkovic M . Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin Med Res. 2007; 5(1):71-82. PMC: 1855336. DOI: 10.3121/cmr.2007.701. View

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(17):2177-88. DOI: 10.2174/092986709788612729. View

Moser V, Tilson H, MacPhail R, BECKING G, Cuomo V, Frantik E . The IPCS Collaborative Study on Neurobehavioral Screening Methods: II. Protocol design and testing procedures. Neurotoxicology. 1997; 18(4):929-38. View

10.

Sakurada K, Matsubara K, Shimizu K, Shiono H, Seto Y, Tsuge K . Pralidoxime iodide (2-pAM) penetrates across the blood-brain barrier. Neurochem Res. 2003; 28(9):1401-7. DOI: 10.1023/a:1024960819430. View

11.

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(6):607-10. DOI: 10.7205/milmed.172.6.607. View

12.

Kassa J, Krejeova G . Neuroprotective effects of currently used antidotes in tabun-poisoned rats. Pharmacol Toxicol. 2003; 92(6):258-64. DOI: 10.1034/j.1600-0773.2003.920602.x. View

13.

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. 2007; 243(3):311-6. DOI: 10.1016/j.tox.2007.10.015. View

14.

Wilhelm C, Snider T, Babin M, Jett D, Platoff Jr G, Yeung D . 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(3):254-65. PMC: 4255143. DOI: 10.1016/j.taap.2014.10.009. View

15.

Kuca K, Juna D, Musilek K . Structural requirements of acetylcholinesterase reactivators. Mini Rev Med Chem. 2006; 6(3):269-77. DOI: 10.2174/138955706776073510. View

16.

Shih T, Duniho S, McDonough J . Control of nerve agent-induced seizures is critical for neuroprotection and survival. Toxicol Appl Pharmacol. 2003; 188(2):69-80. DOI: 10.1016/s0041-008x(03)00019-x. View

17.

Dolgin E . Syrian gas attack reinforces need for better anti-sarin drugs. Nat Med. 2013; 19(10):1194-5. DOI: 10.1038/nm1013-1194. View

18.

Sharma R, Gupta B, Singh N, Acharya J, Musilek K, Kuca K . Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review. Mini Rev Med Chem. 2014; 15(1):58-72. DOI: 10.2174/1389557514666141128102837. View

19.

Jokanovic M . Structure-activity relationship and efficacy of pyridinium oximes in the treatment of poisoning with organophosphorus compounds: a review of recent data. Curr Top Med Chem. 2012; 12(16):1775-89. View

20.

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(4):237-43. DOI: 10.1007/s002040050495. View