A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

Toxicology and Applied Pharmacology

Volumn 281, Issue 3, 2014, Pages 254-265

  Wilhelm, Christina M ^a   Snider, Thomas H ^a   Babin, Michael C ^a   Jett, David A ^b   Platoff, Gennady E ^c   Yeung, David T ^b  

^a BATTELLE MEMORIAL INSTITUTE   (United States)

^b NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^c NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Efficacy; Guinea pig; Intramuscular; Oxime; Toxicity

Indexed keywords

1 (4 CARBAMOYLPYRIDINIO) 1' (2 HYDROXYIMINOMETHYLPYRIDINIO)DIMETHYL ETHER; 1 (HYDROXYIMINO)PROPAN 2 ONE; ANTIDOTE; ATROPINE; CHEMICAL WARFARE AGENT; CHLORPYRIFOS; CHOLINESTERASE; CHOLINESTERASE REACTIVATOR; CYCLOSARIN; METHYLPHOSPHONOTHIOIC ACID S (2 DIISOPROPYLAMINOETHYL) O ETHYL ESTER; OBIDOXIME; ORGANOPHOSPHORUS COMPOUND; OXIME DERIVATIVE; PARAOXON; PESTICIDE; PHORATE; PRALIDOXIME CHLORIDE; SARIN; SOMAN; TABUN; TRIMEDOXIME; UNCLASSIFIED DRUG; [METHOXIME DIMETHANESULFONATE 1,1 METHYLENE BIS[4(HYDROXYIMINO)METHYL]PYRIDINIUM] DIMETHANESULFONATE; [PYRIDINIUM,1 [[[4 (AMINOCARBONYL)PYRIDINIO]METHOXY]METHYL] 2,4 BIS[(HYDROXYIMINO)METHYL], DIMESYLATE; 1 [2,4 BIS(HYDROXYIMINOMETHYL)PYRIDINIO] 1' (4 CARBAMOYLPYRIDINIO)DIMETHYL ETHER DIIODIDE; CHOLINESTERASE INHIBITOR; MUSCARINIC RECEPTOR BLOCKING AGENT; N,N'-MONOMETHYLENEBIS(PYRIDINIUMALDOXIME); OXIME; PYRIDINIUM DERIVATIVE;

ARTICLE; CHOLINESTERASE BLOOD LEVEL; CLINICAL OBSERVATION; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; EVALUATION STUDY; FASCICULATION; FOOD AND DRUG ADMINISTRATION; HARTLEY GUINEA PIG; HEAT EXHAUSTION; LACRIMATION DISORDER; LD 50; LETHALITY; MALE; NONHUMAN; QUALITY OF LIFE; RESPIRATORY DISTRESS; SURVIVOR; TURNOVER TIME; ADVERSE EFFECTS; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; CHEMISTRY; COMBINATION DRUG THERAPY; COMPARATIVE STUDY; DRUG ADMINISTRATION; DRUG MONITORING; GUINEA PIG; INTRAMUSCULAR DRUG ADMINISTRATION; ORGANOPHOSPHATE POISONING; PATHOPHYSIOLOGY; RANDOMIZATION; SUBCUTANEOUS DRUG ADMINISTRATION;

CAVIA;

ANIMALS; ANTIDOTES; ATROPINE; CHEMICAL WARFARE AGENTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASE REACTIVATORS; CHOLINESTERASES; DRUG ADMINISTRATION SCHEDULE; DRUG MONITORING; DRUG THERAPY, COMBINATION; GUINEA PIGS; INJECTIONS, INTRAMUSCULAR; INJECTIONS, SUBCUTANEOUS; MALE; MUSCARINIC ANTAGONISTS; ORGANOPHOSPHATE POISONING; OXIMES; PESTICIDES; PYRIDINIUM COMPOUNDS; RANDOM ALLOCATION;

EID: 84911936585     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2014.10.009     Document Type: Article

References (61)

1. Antonijevic B., Stojiljkovic M.P. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin. Med. Res. 2007, 5(1):71-82.
2. Askew B.M. Oximes and hydroxamic acids as antidotes in anticholinesterase poisoning. Br. J. Pharmacol. Chemother. 1956, 11(4):417-423.
3. Bahar F.G., Ohura K., Ogihara T., Imai T. Species difference of esterase expression and hydrolase activity in plasma. J. Pharm. Sci. 2012, 101(10):3979-3988.
4. Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis and treatment. Adv. Clin. Chem. 2004, 38:151-216.
5. Bajgar J. Treatment and prophylaxis of nerve agent/organophosphates intoxication. Ther. Pharmacol. Clin. Toxicol. 2009, 13:247-253.
6. Bajgar J. Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication. Acta Med. 2010, 53(4):207-211.
7. Baker A. Syrian opposition says deadly chemical attack kills hundreds in Damascus. Time (p. 127, 21-Aug) 2013.
8. Cabal J., Kuca K., Kassa J. Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase. Basic Clin. Pharmacol. Toxicol. 2004, 95:81-86.
9. Cadieux C.L., Broomfield C.A., Kirkpatrick M.G., Kazanski M.E., Lenz D.E., Cerasoli D.M. Comparison of human and guinea pig acetylcholinesterase sequences and rates of oxime-assisted reactivation. Chem. Biol. Interact. 2010, 187(1-3):229-233.
10. Calic M., Lucic-Vrdoljak A., Radic B., Jelic D., Jun D., Kuca K., Kovarik Z. In vitro and in vivo evaluation of pyridinium oximes: mode of interaction with acetylcholinesterase, effect on tabun- and soman-poisoned mice and their cytotoxicity. Toxicology 2006, 219:85-96.
11. Childs A.F., Davies D.R., Green A.L., Rutland J.P. The reactivation by oximes and hydroxamic acids of cholinesterase inhibited by organo-phosphorus compounds. Br. J. Pharmacol. Chemother. 1955, 10(4):462-465.
12. Clement J.G., Hansen A.S., Boulet C.A. Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice. Arch. Toxicol. 1992, 66(3):216-219.
13. Dawson R.M. Review of oximes available for treatment of nerve agent poisoning. J. Appl. Toxicol. 1994, 14(5):317-331.
14. Delfino R.T., Ribeiro T.S., Figueroa-Villar J.D. Organophosphorus compounds as chemical warfare agents: a review. J. Braz. Chem. Soc. 2009, 20:407-428.
15. Dolgin E. Syrian gas attack reinforces need for better anti-sarin drugs. Nat. Med. 2013, 19(10):1194-1195.
16. Dultz L., Epstein M.A., Freeman G., Gray E.H., Weil W.B. Studies on a group of oximes as therapeutic compounds in sarin poisoning. J. Pharmacol. Exp. Ther. 1957, 119:522-531. (4, April).
17. Ekström F., Hörnberg A., Artursson E., Hammarström L.G., Schneider G., Pang Y.P. Structure of HI-6*sarin-acetylcholinesterase determined by X-ray crystallography and molecular dynamics simulation: reactivator mechanism and design. PLoS One 2009, 4(6):e5957.
18. Ellman G.L., Courtney K.D., Andres V., Feather-Stone R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7:88-95.
19. Esposito E.X., Stouch T.R., Wymore T., Madura J.D. Exploring the physicochemical properties of oxime-reactivation therapeutics for cyclosarin, sarin, tabun, and VX inactivated acetylcholinesterase. Chem. Res. Toxicol. 2014, 27(1):99-110.
20. Eyer P., Hagedorn I., Klimmek R., Lippstreu P., Löffler M., Oldiges H., Spöhrer U., Steidl I., Szinicz L., Worek F. HLö 7 dimethanesulfonate, a potent bispyridinium-dioxime against anticholinesterases. Arch. Toxicol. 1992, 66(9):603-621.
21. Eyer P., Radtke M., Worek F. Reactions of isodimethoate with human red cell acetylcholinesterase. Biochem. Pharmacol. 2008, 75:2045-2053.
22. Fleisher J.H., Harris L.W., Miller G.R., Thomas N.C., Cliff W.J. Antagonism of sarin poisoning in rats and guinea pigs by atropine, oximes, and mecamylamine. Toxicol. Appl. Pharmacol. 1970, 16(1):40-47.
23. Hubbard B., Mazzetti M., Landler M. Blasts in the night, a smell, and a flood of Syrian victims 2013, The New York Times, (26-Aug).
24. Inns R.H., Leadbeater L. The efficacy of bispyridinium derivatives in the treatment of organophosphate poisoning in the guinea-pig. J. Pharm. Pharmacol. 1983, 35:427-433.
25. Kassa J. A comparison of the efficacy of new asymmetric bispyridinium oxime BI-6 with other oximes (obidoxime, HI-6) against soman in rats. Hum. Exp. Toxicol. 1998, 17:331-335. (6, June).
26. Kassa J. Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J. Toxicol. Clin. Toxicol. 2002, 40(6):803-816.
27. Kassa J. The influence of the time of antidotal treatment administration on the potency of newly developed oximes to counteract acute toxic effects of tabun in mice. Acta Med. (Hradec Kralove) 2005, 48(2):87-90.
28. Koplovitz L.W., Harris D.R., Anderson W.J., Lennox J.R. Stewart, Reduction of pyridostigmine pretreatment of the efficacy of atropine and 2-PAM Cl treatment of sarin and VX poisoning in rodents. Fundam. Appl. Toxicol. 1992, 18:102-106.
29. Kuca K., Cabal J., Jun D., Bajgar J., Hrabinova M. Potency of new structurally different oximes to reactivate cyclosarin-inhibited human brain acetylcholinesterases. J. Enzym. Inhib. Med. Chem. 2006, 21(6):663-666.
30. Kuca K., Jun D., Bajgar J. Structural factors influencing potency of currently used acetylcholinesterase reactivators for treatment of cyclosarin intoxications. Curr. Pharm. Des. 2007, 13(33):3445-3452. (Review).
31. Kuca K., Musilek K., Stodulka P., Marek J., Hanusova P., Jun D., Hrabinova M., Kassa J., Dolezal B. Twelve different HI-6 salts and their potency to reactivate cyclosarin inhibited AChE in vitro. Lett. Drug Des. Discov. 2007, 4:510-512.
32. Kuca K., Musilek K., Jun D., Pohanka M., Karasova J.Z., Novotny L., Musilova L. Could oxime HI-6 really be considered as "broad-spectrum" antidote?. J. Appl. Biomed. 2009, 7:143-149.
33. Lundy P.M., Hansen A.S., Hand B.T., Boulet C.A. Comparison of several oximes against poisoning by soman, tabun and GF. Toxicology 1992, 72(1):99-105.
34. Lundy P.M., Raveh L., Amitai G. Development of the bisquaternary oxime HI-6 toward clinical use in the treatment of organophosphate nerve agent poisoning. Toxicol. Rev. 2006, 25(4):231-243.
35. Maxwell D.M., Koplovitz I., Worek F., Sweeney R.E. A structure-activity analysis of the variation in oxime efficacy against nerve agents. Toxicol. Appl. Pharmacol. 2008, 231(2):157-164.
36. McGarry K.G., Bartlett R.A., Machesky N.J., Snider T.H., Moyer R.A., Yeung D.T., Brittain M.K. Evaluation of HemogloBind™ treatment for preparation of samples for cholinesterase analysis. Adv. Biosci. Biotechnol. 2013, 4(12):1020-1023.
37. Musilek K., Kuca K., Jun D., Dohnal V., Dolezal M. Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase. J. Enzym. Inhib. Med. Chem. 2005, 20:409-415.
38. Myers D.K. Mechanism of the prophylactic action of diacetylmonoxime against sarin poisoning. Biochim. Biophys. Acta 1959, 34:555-557. (August).
39. Okumura T., Hisaoka T., Naito T., Isonuma H., Okumura S., Miura K., Maekawa H., Ishimatsu S., Takasu N., Suzuki K. Acute and chronic effects of sarin exposure from the Tokyo subway incident. Environ. Toxicol. Pharmacol. 2005, 3:447-450.
40. Oldiges H., Schoene K. Antidotal effects of pyridinium and imidazolium salts on soman and paraoxon poisoning in mice. Arch. Toxikol. 1970, 26:293-305.
41. Radić Z., Sit R.K., Kovarik Z., Berend S., Garcia E., Zhang L., Amitai G., Green C., Radić B., Fokin V.V., Sharpless K.B., Taylor P. Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases. J. Biol. Chem. 2012, 287(15):11798-11809.
42. Rosman Y., Makarovsky I., Bentur Y., Shrot S., Dushnistky T., Krivoy A. Carbamate poisoning: treatment recommendations in the setting of a mass casualties event. Am. J. Emerg. Med. 2009, 27(9):1117-1124.
43. Rutland J.P. The effect of some oximes in sarin poisoning. Br. J. Pharmacol. Chemother. 1958, 13:399-403. (4, December).
44. Schoene K., Oldiges H. Efficacy of pyridinium salts in tabun and sarin poisoning in vivo and in vitro. Arch. Int. Pharmacodyn. Ther. 1973, 204(1):110-123.
45. Shih T.M., Skovira J.W., O'Donnell J.C., McDonough J.H. 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(6-7):386-400.
46. Shih T.M., Skovira J.W., O'Donnell J.C., McDonough J.H. In vivo reactivation by oximes of inhibited blood, brain and peripheral tissue cholinesterase activity following exposure to nerve agents in guinea pigs. Chem. Biol. Interact. 2010, 187:207-214.
47. Shih T.M., Koplovitz I., Kan R.K., McDonough J.H. In search of an effective in vivo reactivator for organophosphorus nerve agent-inhibited acetylcholinesterase in the central nervous system. Adv. Stud. Biol. 2012, 10(4):451-478.
48. Sit R., Radic Z., Gerardi V., Zhang L., Garcia E., Katalinic M., Amitai G., Kovarik Z., Fokin V., Sharpless K.B., Taylor P. New structural scaffolds for centrally acting oxime reactivators of phosphylated cholinesterases. J. Biol. Chem. 2011, 286(22):19422-19430.
49. Skovira J.W., O'Donnell J.C., Koplovitz I., Kan R.K., McDonough J.H., Shih T.M. Reactivation of brain acetylcholinesterase by monoisonitrosoacetone increases the therapeutic efficacy against nerve agents in guinea pigs. Chem. Biol. Interact. 2010, 187(1-3):318-324.
50. Soukup O., Jun D., Tobin G., Kuca K. The summary on non-reactivation cholinergic properties of oxime reactivators: the interaction with muscarinic and nicotinic receptors. Arch. Toxicol. 2013, 87(4):711-719.
51. Stojiljković M.P., Jokanović M. Pyridinium oximes: rationale for their selection as causal antidotes against organophosphate poisonings and current solutions for auto-injectors. Arh. Hig. Rada. Toksikol. 2006, 57(4):435-443.
52. Thiermann H., Mast U., Klimmek R., Eyer P., Hibler A., Pfab R., Felgenhauer N., Zilker T. Cholinesterase status, pharmacokinetics and laboratory findings during obidoxime therapy in organophosphate poisoned patients. Hum. Exp. Toxicol. 1997, 16:473-480.
53. Thiermann H., Worek F., Kehe K. Limitations and challenges in treatment of acute chemical warfare agent poisoning. Chem. Biol. Interact. 2013, 206(3):435-443.
54. US Department of Health Services Human Food and Drug Administration. Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Pharmacol Toxicol. 2005, 05-14456, 7 (July).
55. Vale J.A. Nerve agents: why they are so toxic and can poisoning from these agents be treated?. Toxicology 2009, 240:141-142.
56. Voicu V., Rădulescu F.Ş., Medvedovici A. Toxicological considerations of acetylcholinesterase reactivators. Expert. Opin. Drug Metab. Toxicol. 2013, 9(1):31-50.
57. Wille T., Kaltenbach L., Thiermann H., Worek F. Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates. Chem. Biol. Interact. 2013, 206(3):569-572.
58. Worek F., Thiermann H. The value of novel oximes for treatment of poisoning by organophosphorus compounds. Pharmacol. Ther. 2013, 139(2):249-259.
59. 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.
60. Worek F., Eyer P., Aurbek N., Szinicz L., Thiermann H. Recent advances in evaluation of oxime efficacy in nerve agent poisoning by in vitro analysis. Toxicol. Appl. Pharmacol. 2007, 219(2-3):226-234.
61. Zurer P. Japanese cult used VX to slay member. Chem. Eng. News 1998, 76(35):7.