The Toxicokinetics and Toxicodynamics of Organophosphonates versus the Pharmacokinetics and Pharmacodynamics of Oxime Antidotes: Biological Consequences

Basic and Clinical Pharmacology and Toxicology

Volumn 106, Issue 2, 2010, Pages 73-85

  Voicu, Victor A ^a,b   Thiermann, Horst ^c   Ràdulescu, Flavian Ştefan ^b   Mircioiu, Constantin ^a,b   Miron, Dalia Simona ^b  

^a Army Center for Medical Research   (Romania)

^b CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^c BUNDESWEHR INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 CARBAMOYLPYRIDINIO) 1' (2 HYDROXYIMINOMETHYLPYRIDINIO)DIMETHYL ETHER; 1 [2,4 BIS(HYDROXYIMINOMETHYL)PYRIDINIO] 1' (4 CARBAMOYLPYRIDINIO)DIMETHYL ETHER DIIODIDE; ACETYLCHOLINESTERASE; ANTICONVULSIVE AGENT; ANTIDOTE; ATROPINE; BIS(PYRIDINIUM OXIME) DERIVATIVE; CHOLINESTERASE; CHOLINESTERASE REACTIVATOR; DIHYDROPRALIDOXIME; METHYLPHOSPHONOTHIOIC ACID S (2 DIISOPROPYLAMINOETHYL) O ETHYL ESTER; OBIDOXIME; ORGANOPHOSPHATE; OXIME; PRALIDOXIME; PRALIDOXIME MESILATE; QUATERNARY AMMONIUM DERIVATIVE; SARIN; SOMAN; TABUN; TRIMEDOXIME; UNCLASSIFIED DRUG;

BLOOD BRAIN BARRIER; CELL STRUCTURE; CHOLINERGIC SYSTEM; CHOLINESTERASE INHIBITION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; EXTRACELLULAR SPACE; LIPOPHILICITY; MEMBRANE PERMEABILITY; NONHUMAN; PARTITION COEFFICIENT; PHARMACODYNAMICS; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; SHORT SURVEY; SOLUBILITY; TOXICOKINETICS;

ANIMALS; ANTIDOTES; BLOOD-BRAIN BARRIER; CHOLINESTERASE REACTIVATORS; CHOLINESTERASES; HUMANS; ORGANOPHOSPHORUS COMPOUNDS; OXIMES; TISSUE DISTRIBUTION;

EID: 74549193402     PISSN: 17427835     EISSN: 17427843     Source Type: Journal    
DOI: 10.1111/j.1742-7843.2009.00486.x     Document Type: Short Survey

References (99)

1. Karczmar AG, Usdin E, Wills JH. Anticholinesterase Agents. Pergamon Press, Oxford, 1970.
2. Voicu VA, Mircioiu C, Moldoveanu SC. Finite interactions theory - a biophysical approach to xenobiotic-membrane interactions. In : Sohns T, Voicu VA (eds). NBC Risks - Current Capabilities and Future Perspectives for Protection. Kluwer Academic Publishers, New York, 1999 1 : 95 107.
3. Moldoveanu SC, Voicu VA, Mircioiu C, Moldoveanu B. A theoretical study of the interaction of acetylcholinesterase, irreversible inhibitors, and their antidotes. In : Sohns T, Voicu VA (eds). NBC Risks - Current Capabilities and Future Perspectives for Protection. Kluwer Academic Publishers, New York, 1999 1 : 109 125.
4. 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.
5. Voicu VA, Olinescu R. Enzymatic Mechanisms in Pharmacodynamics. Abacus Press, Tunbridge Wells, Kent, UK, 1977.
6. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995 12 : 413 420.
7. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: Transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res 2005 22 : 11 23.
8. Fagerholm U. The role of permeability in drug ADME/PK, interactions and toxicity-presentation of a permeability-based classification system (PCS) for prediction of ADME/PK in humans. Pharm Res 2008 25 : 625 638.
9. Clark DE, Grootenhuis PD. Progress in computational methods for the prediction of ADMET properties. Curr Opin Drug Discov Devel 2002 5 : 382 390.
10. van den Waterbeemd H, Gifford E. ADMET in silico modelling: towards prediction paradise? Nat Rev Drug Discov 2003 2 : 192 204.
11. Thiermann H, Kehe K, Steinritz D, Mikler J, Hill I, Zilker T et al. Red blood cell acetylcholinesterase and plasma butyrylcholinesterase status: important indicators for the treatment of patients poisoned by organophosphorus compounds. Arh Hig Rada Toksikol 2007 58 : 359 366.
12. Cokug̀raş AN. Butyrylcholinesterase: structure and physiological importance. Turk J Biochem 2003 28 : 54 61.
13. Glynn P. Neuropathy target esterase. Biochem J 1999 344 : 625 631.
14. Voicu VA, Jiquidi M, Ionescu-Visan I, Bruja N. Noncholinergic biochemical effects of some OP anticholinesterasics. Rev San Milit 1980 4 : 449 454.
15. Thomson ChM, Richardson RJ. Anticholinesterase insecticides. In : Marrs TC, Ballantine B (eds). Pesticide Toxicology and International Regulation. John Willey and Sons, Chichester 2004 89 93.
16. Palyulin VA, Radchenko EV, Baskin II, Makhaeva GF, Zefirov NS. Modelling the multi-target selectivity: o-phosphorylated oximes as serine hydrolase inhibitors. Chem Central J 2009 S1 : 23 30.
17. Tracey KJ. The inflammatory reflex. Nature 2002 420 : 853 859.
18. Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 2007 117 : 289 296.
19. Lotti M. Cholinesterase inhibition: complexities in interpretation. Clin Chem 1995 41 : 1814 1818.
20. Munro N. Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: implications for public protection. Environ Health Perspect 1994 102 : 18 37.
21. Jiquidi M, Voicu VA, Ionescu-Visan I, Mircioiu C. Changes of toxicodynamic and toxicokinetics parameters of paraoxone by obidoxime (Roum.). Rev San Milit 1980 2 : 182 188.
22. Antonijevic B, Stojiljkovic MP. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin Med Res 2007 5 : 71 82.
23. Sidell FR, Takafuji ET, Franz DR. Medical Aspects of Chemical and Biological Warfare, Chap.5. Borden Inst. W.R.A.M.C., Washington, DC, 1997 138 141.
24. Lotti M. The pathogenesis of organophosphate polyneuropathy. Crit Rev Toxicol 1991 21 : 465 487.
25. Maxwell DM, Brecht KM, Koplovitz I, Sweeney RE. Acetylcholinesterase inhibition: does it explain the toxicity of organophosphorus compounds? Arch Toxicol 2006 80 : 756 760.
26. Rothan SM, Olney JW. Excitotoxicity and NMDA receptors 1987. TINS 1987 10 : 299 302.
27. Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA. NMDA antagonist neurotoxicity: mechanism and prevention. Science 1991 254 : 1515 1518.
28. Lee JM, Grabb MC, Zipfel GJ, Choi DW. Brain tissue responses to ischemia. J Clin Invest 2000 106 : 723 731.
29. Marculescu Z, Pociu A, Voicu VA, Hinescu ME. Cell death in rat brain after low-dose exposure to paraoxon. Rev Roum Biol 2001 46 : 69 97.
30. Solberg Y, Belkin M. The role of excitotoxicity in organophosphorous nerve agents central poisoning. Trends Pharmacol Sci 1997 18 : 183 185.
31. McDonough JH Jr., Shih TM. Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev 1997 21 : 559 579.
32. van den Beukel I, Dijcks FA, Vanderheyden P, Vauquelin G, Oortgiesen M. Differential muscarinic receptor binding of acetylcholinesterase inhibitors in rat brain, human brain and Chinese hamster ovary cells expressing human receptors. J Pharmacol Exp Ther 1997 281 : 1113 1119.
33. Bakry NM, el-Rashidy AH, Eldefrawi AT, Eldefrawi ME. Direct actions of organophosphate anticholinesterases on nicotinic and muscarinic acetylcholine receptors. J Biochem Toxicol 1988 3 : 235 259.
34. Santos MD, Pereira EF, Aracava Y, Castro NG, Fawcett WP, Randall WR et al. Low concentrations of pyridostigmine prevent soman-induced inhibition of GABAergic transmission in the central nervous system: involvement of muscarinic receptors. J Pharmacol Exp Ther 2003 304 : 254 265.
35. Mileson BE, Chambers JE, Chen WL, Dettbarn W, Ehrich M, Eldefrawi AT et al. Common mechanism of toxicity: a case study of organophosphorus pesticides. Toxicol Sci 1998 41 : 8 20.
36. Smulders CJ, Bueters TJ, Vailati S, van Kleef RG, Vijverberg HP. Block of neuronal nicotinic acetylcholine receptors by organophosphate insecticides. Toxicol Sci 2004 82 : 545 554.
37. Johnson PS, Michaelis EK. Characterization of organophosphate interactions at N-methyl-D-aspartate receptors in brain synaptic membranes. Mol Pharmacol 1992 41 : 750 756.
38. Barone S Jr., Das KP, Lassiter TL, White LD. Vulnerable processes of nervous system development: a review of markers and methods. Neurotoxicology 2000 21 : 15 36.
39. Shih TM, Koviak TA, Capacio BR. Anticonvulsants for poisoning by the organophosphorus compound soman: pharmacological mechanisms. Neurosci Biobehav Rev 1991 15 : 349 362.
40. Marrs T, Maynard RL, Sidell FR. Chemical Warfare Agents - Toxicology and Treatment. John Wiley & Sons, Chichester 1996.
41. Shih TM, Duniho SM, McDonough JH. Control of nerve agent-induced seizures is critical for neuroprotection and survival. Toxicol Appl Pharmacol 2003 188 : 69 80.
42. Lallement G, Pernot-Marino I, Baubichon D, Burckhart MF, Carpentier P, Blanchet G. Modulation of soman-induced neuropathology with an anticonvulsant regimen. Neuroreport 1994 5 : 2265 2268.
43. Shih TM, McDonough JH Jr. Organophosphorus nerve agents-induced seizures and efficacy of atropine sulfate as anticonvulsant treatment. Pharmacol Biochem Behav 1999 64 : 147 153.
44. Shih TM, Kan RK, McDonough JH. In vivo cholinesterase inhibitory specificity of organophosphorus nerve agents. Chem Biol Interact 2005 158 : 293 303.
45. Shih TM, Rowland TC, McDonough JH. Anticonvulsants for nerve agent-induced seizures: the influence of the therapeutic dose of atropine. J Pharmacol Exp Ther 2007 320 : 154 161.
46. Carpantier P, Testylier G, Baille V, Dhote F, Job A, Pouytos B et al. Soman-induced seizures and related brain damage: how to treat seizures and assess their effects non-invasively? J Med CBR Def 2008 6 : 1 16.
47. Pawley AC, Flesher S, Boegman RJ, Beninger RJ, Jhamandas KH. Differential action of NMDA antagonists on cholinergic neurotoxicity produced by N-methyl-D-aspartate and quinolinic acid. Br J Pharmacol 1996 117 : 1059 1064.
48. Globus MY, Ginsberg MD, Busto R. Excitotoxic index-a biochemical marker of selective vulnerability. Neurosci Lett 1991 127 (1 39 42.
49. Voicu VA, Miu C, Jiquidi M, Furnica C, Elian I. RO Patent 79914, Medicine for control and treatment of toxic effects of organic-phosphoric compounds. 1974.
50. Lorke DE, Kalasz H, Petroianu GA, Tekes K. Entry of oximes into the brain: a review. Curr Med Chem 2008 15 : 743 753.
51. Hitchcock StA, Pennington LD. Structure-brain exposure relationship. J Med Chem 2006 49 : 7559 7583.
52. Gearhart JM, Jepson GW, Clewell HJ, Andersen ME, Conolly RB. Physiologically based pharmacokinetic model for the inhibition of acetylcholinesterase by organophosphate esters. Environ Health Perspect 1994 S11 : 51 60.
53. Czerwinski SE, Skvorak JP, Maxwell DM, Lenz DE, Baskin SI. Effect of octanol:water partition coefficients of organophosphorus compounds on biodistribution and percutaneous toxicity. J Biochem Mol Toxicol 2006 20 : 241 246.
54. Craig FN, Cummings EG, Sim VM. Environmental temperature and the percutaneous absorption of cholinesterase inhibitor, Vx. J Invest Dermatol 1977 68 : 357 361.
55. Aurbek N, Thiermann H, Szinicz L, Eyer P, Worek F. Application of kinetic-based computer modelling to evaluate the efficacy of HI 6 in percutaneous VX poisoning. Toxicology 2006 224 : 74 80.
56. Sidell FR, Groff WA. The reactivatibility of cholinesterase inhibited by VX and sarin in man. Toxicol Appl Pharmacol 1974 27 : 241 252.
57. Kuca K, Cabal J, Kassa J, Jun D, Hrabinová M. Comparison of in vitro potency of oximes (pralidoxime, obidoxime, HI-6) to reactivate sarin-inhibited acetylcholinesterase in various parts of pig brain. J Appl Toxicol 2005 25 : 271 276.
58. De Jong LPA, Verhagen MAA, Langenberg JP, Hagedorn I, Löffler M. The bispyridinium-dioxime Hlö-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman. Biochem Pharmacol 1989 38 : 633 640.
59. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001 46 : 3 26. (Pubitemid 33653411)
60. Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx 2005 2 : 541 553.
61. Hansch C, Leo A, Mekapati SB, Kurup A. QSAR and ADME. Bioorg Med Chem 2004 12 : 3391 3400.
62. Osterberg T, Norinder U. Prediction of polar surface area and drug transport processes using simple parameters and PLS statistics. J Chem Inf Comput Sci 2000 40 : 1408 1411.
63. Suomalainen P, Johans C, Sdelund T, Kinnunen PK. Surface activity of drugs applied to the prediction of BBB permeability. J Med Chem 2004 47 : 1783 1788.
64. Fischer H, Gottschlich R, Seelig A. Blood-brain barrier permeation: molecular parameters governing passive diffusion. J Membr Biol 1998 165 : 201 211.
65. Millard CB, Broomfield CA. Anticholinesterases: medical applications of neurochemical principles. J Neurochem 1995 64 : 1909 1918.
66. Cassel G, Karlsson L, Waara L, Ang KW, Göransson-Nyberg A. Pharmacokinetics and effects of HI 6 in blood and brain of soman-intoxicated rats: a microdialysis study. Eur J Pharmacol 1997 332 : 43 52.
67. Czerwinski SE, Maxwell DM, Lenz DE. A method for measuring octanol:water partition coefficients of highly toxic organophosphorus compounds. Toxicol Mech Methods 1998 8 : 39 149.
68. Aurbek N, Thiermann H, Szinicz L, Eyer P, Worek F. Analysis of inhibition, reactivation and aging kinetics of highly toxic organophosphorus compounds with human and pig acetylcholinesterase. Toxicology 2006 224 : 91 9.
69. Jokanović M, Stojiljković MP. Current understanding of the application of pyridinium oximes as cholinesterase reactivators in treatment of organophosphate poisoning. Eur J Pharmacol 2006 553 : 10 7.
70. Csermely T, Kalász H, Petroianu GA, Kuca K, Darvas F, Ludányi K et al. Analysis of pyridinium aldoximes - a chromatographic approach. Curr Med Chem 2008 15 : 2401 2418.
71. Voicu VA, Jiquidi M, Sitcai N, Bruja N. Some pharmacological correlations of hypothermia induced by anticholinesterases. Rev Roum Physiology 1976 13 : 285 291.
72. Su CT, Wang PH, Liu RF, Shih JH, Ma C, Lin CH et al. Kinetic studies and structure-activity relationships of bispyridinium oximes as reactivators of acetylcholinesterase inhibited by organophosphorus compounds. Fundam Appl Toxicol 1986 6 : 506 514.
73. Lundy PM, Goulet JC, Hand BT. Hormone- and dose schedule-dependent protection by HI-6 against soman and tabun poisoning. Fundam Appl Toxicol 1989 12 : 595 603.
74. Clement JG. Central activity of acetylcholinesterase oxime reactivators. Toxicol Appl Pharmacol 1992 112 : 104 109.
75. Bodor N, Shek E, Higuchi T. Improved delivery through biological membranes. 1. Synthesis and properties of 1-methyl-1,6-dihydropyridine-2- carbaldoxime, a pro-drug of N-methylpyridinium-2-carbaldoxime chloride. J Med Chem 1976 19 : 102 107.
76. Lorke DE, Kalasz H, Petroianu GA, Tekes K. Entry of oximes into the brain: a review. Curr Med Chem 2008 15 (8 743 753.
77. Rousseaux CG, Dua AK. Pharmacology of HI-6, an H-series oxime. Can J Physiol Pharmacol 1989 67 : 1183 1189.
78. Kusić R, Bosković B, Vojvodić V, Jovanović D. HI-6 in man: blood levels, urinary excretion, and tolerance after intramuscular administration of the oxime to healthy volunteers. Fundam Appl Toxicol 1985 5 : S89 97.
79. Bajgar J, Hajek P, Slizova D, Krs O, Fusek J, Kuca K et al. Changes of acetylcholinesterase activity in different rat brain areas following intoxication with nerve agents: biochemical and histochemical study. Chem Biol Interact 2007 165 : 14 21.
80. Firemark H, Barlow CF, Roth LJ. The penetration of 2-PAM-C14 into brain and the effect of cholinesterase inhibitors on its transport. J Pharmacol Exp Ther 1964 145 : 252 265.
81. Falb A, Erdmann WD. Penetration of 14C-obidoxime through the so-called blood-brain barrier of mice and rats. Arch Toxicol 1969 24 : 123 132.
82. Worek F, Aurbek N, Thiermann H. Reactivation of organophosphate-inhibited human AChE by combinations of obidoxime and HI 6 in vitro. J Appl Toxicol 2007 27 : 582 588.
83. Kassa J, Kuca K, Karasova J, Musilek K. The development of new oximes and the evaluation of their reactivating, therapeutic and neuroprotective efficacy against tabun. Mini Rev Med Chem 2008 8 : 1134 1143.
84. Lundy PM, Hansen AS, Hand BT, Boulet CA. Comparison of several oximes against poisoning by soman, tabun and GF. Toxicology 1992 72 : 99 105.
85. van Helden HP, van der Wiel HJ, Zijlstra JJ, Melchers BP, Busker RW. Comparison of the therapeutic effects and pharmacokinetics of HI-6, HLö-7, HGG-12, HGG-42 and obidoxime following non-reactivatable acetylcholinesterase inhibition in rats. Arch Toxicol 1994 68 : 224 230.
86. Kassa J, Jun D, Kuca K. The reactivating and therapeutic efficacy of oximes to counteract Russian VX poisonings. Int J Toxicol 2006 25 : 397 401.
87. 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.
88. Rump S, Kowalczy M. Management of convulsion in nerve agent acute poisoning: a polish perspective. J Med CBR Def 2004 1 : 1 14.
89. Bodor N, Shek E, Higuchi T. Delivery of a quaternary pyridinium salt across the blood-brain barrier by its dihydropyridine derivative. Science 1975 190 : 155 156.
90. Silva GR, Borges I, Figueroa-Villar JD. DFT conformational studies of the HI-6 molecule. In J Quant Chem 2005 105 : 260 269.
91. Erdmann WD, Engelhard H. Pharmacologic-toxicologic studies with the dichloride of bis-(4-hydroxyiminomethyl-1-pyridinium-methyl)-ether, a new esterase reactivator. Arzneimittelforsch 1964 14 : 5 11.
92. Ellin RI, Wills JH. Oximes antagonistic to inhibitors of cholinesterase. II. J Pharm Sci 1964 53 : 1143 1150.
93. Marrs TC. Toxicology of oximes used in treatment of organophosphate poisoning. Adverse Drug React Toxicol Rev 1991 10 : 61 73.
94. Wills JH. Treatment of poisoning by anticholinesterases. In : Karczmar AG (ed International Encyclopedia of Pharmacology and Therapeutics, Sect.13 (Anticholinersterase Agents). Pergamon, Oxford, 1970 1 : 414 429.
95. Kepner LA, Wolthuis OL. A comparison of the oximes HS-6 and HI-6 in the therapy of soman intoxication in rodents. Eur J Pharmacol 1978 48 : 377 382.
96. Castro AT, Fugueroa-Villar JD. Molecular structure, conformational analysis and change distribution of pralidoxime: Ab initio and DFT studies. Int J Quantum Chem 2002 89 : 135.
97. 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 6.
98. Dearden JC. Partitioning and lipophilicity in quantitative structure-activity relationships. Environ Health Perspect 1985 61 : 203 228.
99. Campbell DB. The use of kinetic-dynamic interactions in the evaluation of drugs. Psychopharmacology (Berl) 1990 100 : 433 450.