Comparison of Cholinesterases and Carboxylesterase as Bioscavengers for Organophosphorus Compounds

  • Donald M. Maxwell
  • Karen Brecht
  • Ashima Saxena
  • Shawn Feaster
  • B. P. Doctor


Inasmuch as the traditional pharmacological approaches to protection against organophosphorus (OP) compounds may be near their practical limits, a new approach using enzymes as bioscavengers has recently been examined. The feasibility of using bioscavengers, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CaE), to provide protection against OP compounds has been demonstrated in rodents as well as nonhuman primates (1–5). The major advantages of bioscavengers for protection against OP toxicity are their rapid removal of OP compounds from circulation, their selective reactivities with the toxic stereoisomers of chiral compounds, and their relatively slow clearance from circulation. In comparison to other pharmacological approaches, the appeal of bioscavenger protection is that bioscavenger-protected survivors of exposure to OP compounds do not exhibit the postexposure incapacitation and toxic effects that are commonly observed with survivors protected by traditional antidotal approaches, such as oximes, anticholinergics, or carbamates (6).


Bulky Group Spontaneous Reactivation 2Walter Reed Army Institute Cationic Inhibitor Serum BChE 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Doctor, B. P.; Raveh, L.; Wolfe, A. D.; Maxwell, D. M.; Ashani, Y. Neurosci. Biobehav. Rev. 1991, 15, 123–128.PubMedCrossRefGoogle Scholar
  2. 2.
    Broomfield, C. A.; Maxwell, D. M.; Solana, R. P.; Castro, C. A.; Finger, A. V.; Lenz, D. E. J. Pharmacol. Exp. Therap. 1991, 259, 633–638.Google Scholar
  3. 3.
    Maxwell, D. M.; Castro, C. A.; De La Hoz, D. M.; Gentry, M. K.; Gold, M. B.; Solana, R. P.; Wolfe, A. D.; Doctor, B. P. Toxicol. Appl. Pharmacol. 1992, 115, 44–49.PubMedCrossRefGoogle Scholar
  4. 4.
    Doctor, B. P.; Blick, D. W.; Caranto, G.; Castro, C. A.; Gentry, M. K.; Larrison, R.; Maxwell, D. M.; Murphy, M. R.; Schutz, M.; Waibel, K.; Wolfe, A. D. Chem.-Biol. Interact. 1993, 87, 285–293.PubMedCrossRefGoogle Scholar
  5. 5.
    Raveh, L; Grauer, E.; Grunwald, J.; Cohen, E.; Ashani, Y. Toxicol. Appl. Pharmacol. 1997, 145, 43–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Maxwell, D. M.; Brecht, K. M.; Doctor, B.P.; Wolfe, A. D. J. Pharmacol. Exp. Therap. 1993, 264, 1085–1089.Google Scholar
  7. 7.
    Cygler, M.; Schrag, J. D.; Sussman, J. C; Harel, M.; Silman, L; Gentry, M. K.; Doctor, B. P. Protein Sci. 1993, 2, 366–382.PubMedCrossRefGoogle Scholar
  8. 8.
    Maxwell, D. M.; Doctor, B. P. In Chemical Warfare Agents: S. M. Somani, Ed.; Academic Press: San Diego, CA, 1992: pp. 195–207.Google Scholar
  9. 9.
    Caranto, G. R.; Waibel, K. H.; Asher, J. M.; Larrison, R. W; Brecht, K. M.; Schutz, M. B.; Raveh, L.; Ashani, Y.; Wolfe, A. D.; Maxwell, D. M.; Doctor, B. P. Biochem. Pharmacol. 1994, 47, 347–357.PubMedCrossRefGoogle Scholar
  10. 10.
    Saxena, A.; Redman, A. M. G.; Jiang, X.; Lockridge, O.; Doctor, B. P. Biochemistry 1997, 36, 14642–14651.PubMedCrossRefGoogle Scholar
  11. 11.
    Sussman, J. L.; Harel, M.; Frolow, F.; Oefner, C; Goldman, A.; Toker, L.; Silman, I. Science 1991, 253, 872–879.PubMedCrossRefGoogle Scholar
  12. 12.
    Harel, M.; Sussman, J. L.; Krejci, E.; Bon, S.; Chanal, P.; Massoulie, J.; Silman, I. Proc. Natl. Acad. Sci. USA 1992, 89, 10827–10831.PubMedCrossRefGoogle Scholar
  13. 13.
    Schrag, J. D.; Li, Y; Wu, S.; Cygler, M. Nature 1991, 351, 761–765.PubMedCrossRefGoogle Scholar
  14. 14.
    Ripoll, D. R.; Faerman, C. H.; Axelsen, P.; Silman, I.; Sussman, J. L. Proc. Natl. Acad. Sci. USA 1993, 90, 5128–5132.PubMedCrossRefGoogle Scholar
  15. 15.
    Shafferman, A.; Ordentlich, A.; Barak, D.; Kronman, C; Ber, R.; Bino, T.; Ariel, N.; Osman, R.; Velan, B. EMBO J. 1994, 13, 3448–3455.PubMedGoogle Scholar
  16. 16.
    Keijer, J. H.; Wolring, G. Z. Biochim. Biophys. Acta 1969, 185, 465–468.PubMedCrossRefGoogle Scholar
  17. 17.
    Langenberg, J. P.; Van Dijk, C; Sweeney, R. E.; Maxwell, D. M.; De Jong, L. P. A.; Benschop, H. P. Arch. Toxicol. 1997, 71, 320–331.PubMedCrossRefGoogle Scholar
  18. 18.
    Benschop, H. P.; Berends, F.; De Jong, L. P. A. Fundam. Appl. Toxicol. 1981, 1, 177–182.PubMedCrossRefGoogle Scholar
  19. 19.
    Maxwell, D. M.; Brecht, K. M.; O’Neill, B. L. Toxicol. Lett. 1987, 39, 35–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Due, A. H.; Trap, H. C; Van Der Weil, H. J.; Benschop, H. P. Arch. Toxicol. 1993, 67, 706–711.PubMedCrossRefGoogle Scholar
  21. 21.
    Ordentlich, A.; Kronman, C; Barak, D.; Stein, D.; Ariel, N.; Marcus, D.; Velan, B.; Shafferman, A. FEBS Lett. 1993, 334, 215–220.PubMedCrossRefGoogle Scholar
  22. 22.
    Shafferman, A.; Ordentlich, A.; Barak, D.; Stein, D.; Ariel, N.; Velan, B. Biochem. J. 1996, 318, 833–840.PubMedGoogle Scholar
  23. 23.
    Masson, P.; Froment, M. T.; Bartels, C. F.; Lockridge, O. Biochem. J. 1997, 325, 53–61.PubMedGoogle Scholar
  24. 24.
    Millard, C. B.; Lockridge, O.; Broomfield, C. A. Biochemistry 1995, 34, 15925–15933.PubMedCrossRefGoogle Scholar
  25. 25.
    Newcomb, R. D.; Campbell, P. M.; Ollis, D. L.; Cheah, E.; Russell, R. J.; Oakeshott, J. G. Proc. Natl. Acad. Sci. USA 1997, 94, 7464–7468.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Donald M. Maxwell
    • 1
  • Karen Brecht
    • 1
  • Ashima Saxena
    • 2
  • Shawn Feaster
    • 2
  • B. P. Doctor
    • 2
  1. 1.U. S. Army Medical Research Institute of Chemical DefenseAberdeen Proving GroundUSA
  2. 2.Walter Reed Army Institute of ResearchUSA

Personalised recommendations