An evaluation of reactivating and therapeutic efficacy of newly developed oximes (K206, K269) and commonly used oximes (obidoxime, HI-6) in cyclosarin-poisoned rats and mice

Clinical Toxicology

Volumn 47, Issue 1, 2009, Pages 72-76

  Kassa, Jiri ^a,b   Karasova, Jana ^a   Musilek, Kamil ^a   Kuca, Kamil ^a   Bajgar, Jiri ^a  

^a UNIVERSITY OF DEFENCE   (Czech Republic)

^b UNIVERSITY OF DEFENCE   (Czech Republic)

Author keywords

Acetylcholinesterase; Cyclosarin; HI 6; K206; K269; Mice; Obidoxime; Rats; Reactivation

Indexed keywords

1 (3 CARBAMOYLPYRIDINIUM) 4 (4 HYDROXYIMINOMETHYLPYRIDINIUM)BUT 2 ENE DIBROMIDE; 1 (4 CARBAMOYLPYRIDINIO) 1' (2 HYDROXYIMINOMETHYLPYRIDINIO)DIMETHYL ETHER; 1 [4 (1 AMINOHYDROXYIMINOMETHYL)PYRIDINIUM] 4 (4 HYDROXYIMINOMETHYLPYRIDINIUM)BUT 2 ENE DIBROMIDE; ACETYLCHOLINE; ACETYLCHOLINESTERASE; CYCLOSARIN; K 269; OBIDOXIME; OXIME DERIVATIVE; TIPINDOLE METHIODIDE; UNCLASSIFIED DRUG; 1 (3 CARBAMOYLPYRIDINIUM) 4 (4 HYDROXYIMINOMETHYLPYRIDINIUM) BUT 2 ENE; 1 (4 (1 AMINOHYDROXYIMINOMETHYL)PYRIDINIUM) 4 (4 HYDROXYIMINOMETHYLPYRIDINIUM) BUT 2 ENE; 1-(3-CARBAMOYLPYRIDINIUM)-4-(4-HYDROXYIMINOMETHYLPYRIDINIUM)-BUT-2-ENE; 1-(4-(1-AMINOHYDROXYIMINOMETHYL)PYRIDINIUM)-4-(4-HYDROXYIMINOMETHYLPYRIDINIUM)-BUT-2-ENE; ATROPINE; CHEMICAL WARFARE AGENT; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; CHOLINESTERASE REACTIVATOR; ORGANOPHOSPHORUS COMPOUND; OXIME; PYRIDINIUM DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CALCULATION; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; ENZYME INHIBITION; ENZYME REACTIVATION; INTOXICATION; MALE; MOUSE; NONHUMAN; RAT; ANIMAL; BLOOD; BRAIN; CHEMICAL STRUCTURE; CHEMISTRY; DIAPHRAGM; DRUG COMBINATION; ENZYMOLOGY; LD 50; METABOLISM; MOUSE STRAIN; TREATMENT OUTCOME; WISTAR RAT;

MUS; RATTUS;

ANIMALS; ATROPINE; BRAIN; CHEMICAL WARFARE AGENTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASE REACTIVATORS; CHOLINESTERASES; DIAPHRAGM; DRUG THERAPY, COMBINATION; LETHAL DOSE 50; MALE; MICE; MICE, INBRED STRAINS; MOLECULAR STRUCTURE; OBIDOXIME CHLORIDE; ORGANOPHOSPHORUS COMPOUNDS; OXIMES; POISONING; PYRIDINIUM COMPOUNDS; RATS; RATS, WISTAR; TREATMENT OUTCOME;

EID: 59649112693     PISSN: 15563650     EISSN: 15569519     Source Type: Journal    
DOI: 10.1080/15563650802043652     Document Type: Article

References (26)

1. Marrs TC. Organophosphate poisoning. Pharmacol Ther 1993; 58:51-66.
2. Lotti M. Organophosphorus compounds. In: Spencer PS, Schaumburg HH, eds. Experimental and Clinical Neurotoxicology. New York: Oxford University Press; 2000: 898-925.
3. Dawson RM. Review of oximes available for treatment of nerve agent poisoning. J Appl Toxicol 1994; 14:317-331.
4. Taylor P. Anticholinesterase agents. In: Hardman JG, Limbird LE, eds. The Pharmacological Basis of Therapeutics. New York: McGraw Hill; 1996: 161-176.
5. Shih TM. Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity. Arch Toxicol 1993; 67:637-646.
6. Worek F, Backer M, Thiermann H, Szinicz L, Mast U, Klimmek R, Eyer P. Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning. Hum Exp Toxicol 1997; 16:466-472.
7. Kassa J. Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J Toxicol Clin Toxicol 2002; 40:803-816.
8. Bajgar J. Organophosphate/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 2004; 38:151-216.
9. Musilek K, Holas O, Jun D, Dohnal V, Gunn-Moore F, Opletalova V, Dolezal M, Kuca K. Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker - preparation and reactivation of tabun and paraoxon-inhibited acetylcholinesterase. Bioorg Med Chem 2007; 15: 6733-6741.
10. Musilek K, Holas O, Kuca K, Jun D, Dohnal V, Opletalova V, Dolezal M. Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase. J Enzyme Inhib Med Chem 2008; 23:70-76; doi: 10.1080/14756360701383981.
11. Kassa J, Cabal J. A comparison of the efficacy of acetylcholinesterase reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods. Pharmacol Toxicol 1999; 84:41-45.
12. Tallarida R, Murray R. Manual of Pharmacological Calculation with Computer Programs. New York: Springer-Verlag; 1987.
13. Clement JG, Hansen AS, Boulet CA. Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice. Arch Toxicol 1992; 66:216-219.
14. Ellman GL, Courtney DK, Andres V Jr, Featherstone RM. 1961. A new and rapid determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7:88-93.
15. Kuca K, Jun D, Musilek K. Structural requirements of acetylcholinesterase reactivators. Mini Rev Med Chem 2006; 6:269-277.
16. Kuca K, Racakova V, Jun D, Bajgar J. Structure-activity relationship of acetylcholinesterase reactivators - antidotes against nerve agents. Lett Org Chem 2007; 4:212-217.
17. Kassa J, Cabal J. A comparison of the efficacy of a new asymmetric bispyridinium oxime BI-6 with presently used oximes and H oximes against sarin by in vitro and in vivo methods. Hum Exp Toxicol 1999; 18:560-565.
18. Kuca K, Jun D, Bajgar J. Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro. Drug Chem Toxicol 2007; 30:31-40.
19. 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; 72:237-243.
20. Kuca K, Musilek K, Paar M, Jun D, Stodulka P, Hrabinova M, Marek J. Targeted synthesis of 1-(4-hydroxyiminomethylpyridinium)-3-pyridinium propane dibromide - a new nerve agent reactivator. Molecules 2007; 12:1964-1972.
21. 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; 132:111-118.
22. Kuca K, Cabal J, Jun D, Kassa J, Bartosova L, Kunesova G. In vitro reactivation potency of some acetylcholinesterase reactivators against sarin- and cyclosarin-induced inhibitions. J Appl Toxicol 2005; 25:296-300.
23. Kuca J, Patocka J. Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium-oximes. J Enzyme Inhib Med Chem 2004; 19:39-43.
24. 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; 59:795-798.
25. Kassa J, Kuca K, Bartosova L, Kunesova G. The development of new structural analogues of oximes for the antidotal treatment of poisoning by nerve agents and the comparison of their reactivating and therapeutic efficacy with currently available oximes. Cur Org Chem 2007; 11:267-283.
26. Kassa J, Karasova J, Bajgar J, Kuca K, Musilek K. A comparison of the therapeutic and reactivating efficacy of newly developed bispyridinium compounds (K206, K269) with currently available oximes against tabun in rats and mice. J Enzyme Inhib Med Chem 2008; doi: 10.1080/14756360701809902.