J Appl Biomed 2:163-167, 2004 | DOI: 10.32725/jab.2004.019

The therapeutic efficacy of oxime treatment in cyclosarin-poisoned mice pretreated with a combination of pyridostigmine benactyzine and trihexyphenidyl

Lucie Ševelová*, Kamil Kuča, Gabriela Krejčová, Josef Vachek
Purkyně Military Medical Academy, Department of Toxicology, Hradec Králové, Czech Republic

The present study was performed to assess and compare the therapeutic efficacy of various oximes (methoxime, BI-6, HI-6) combined with benactyzine (BNZ) in cyclosarin (GF-agent)-poisoned mice and to evaluate the influence of pretreatment with PANPAL (pyridostigmine, benactyzine and trihexyphenidyl) on the effect of antidotal treatment in mice poisoned with the GF-agent. In the first part of our experiment, methoxime, BI-6 or HI-6 in combination with benactyzine were used for the treatment of GF-poisoned mice. In the second part of the experiment the animals were pretreated with PANPAL 60 min before the GF-agent challenge and then the oxime therapy was applied in the same time scheme as before. All the therapeutic regimens showed a protective ratio higher than 2 and significantly increased the LD50 of GF-agent. The most efficacious oxime in decreasing of GF-agent toxicity was HI-6. PANPAL increased the protective ratios of all therapeutic regimens in comparison with administration of the oxime and BNZ alone. From the results obtained, the combination of pretreatment with PANPAL and following therapy with BNZ and HI-6 seems to be the most efficacious therapeutic regimen for treatment of GF-agent-poisoned mice.

Keywords: GF-agent; cyclosarin; benactyzine; pyridostigmine; PANPAL; oxime

Received: January 30, 2004; Revised: March 20, 2004; Published: July 31, 2004  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Ševelová L, Kuča K, Krejčová G, Vachek J. The therapeutic efficacy of oxime treatment in cyclosarin-poisoned mice pretreated with a combination of pyridostigmine benactyzine and trihexyphenidyl. J Appl Biomed. 2004;2(3):163-167. doi: 10.32725/jab.2004.019.
Download citation

References

  1. Abou-donia M.B., L.B. Goldstein, K.H. Jones, A.A. Abdel-Rahman, T.V. Damodaran, A.M. Dechkovskaia, S.L. Bullman, B.E. Amir, W.A. Khan: Locomotor and sensimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination. Toxicol. Sci. 60: 305-314, 2001. Go to original source... Go to PubMed...
  2. Bajgar J., J. Fusek, J. Vachek: Treatment and prophylaxis against nerve agent poisoning. ASA Newsl. 94: 10-11, 1994.
  3. Berry W.K. and D.R. Davis: The use of carbamates and atropine in the protection of animals against poisoning with 1,2,2-trimethylpropylmethylphosphonofluoridate. Biochem. Pharmacol. 19: 927-934, 1970. Go to original source... Go to PubMed...
  4. Gouge S.F, D.J. Daniels, C.E. Smith: Exacerbation of asthma after pyridostigmine during Operation Desert Storm. Mil. Med. 159: 108-111, 1994. Go to original source... Go to PubMed...
  5. Kassa J.: Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J. Toxicol. 40: 803-816, 2002. Go to original source... Go to PubMed...
  6. Kassa J.: The influence of anticholinergic drug selection on the effectiveness of oximes against soman-induced supralethal poisoning in mice. Acta Medica (Hradec Králové) 44: 77-79, 2001. Go to original source... Go to PubMed...
  7. Kassa J. and J. Bajgar: Comparison of the efficacy of HI-6 and obidoxime against cyclohexyl methylphosphonofluoridate (GF) in rats. Hum. Exp. Toxicol. 14: 923-928, 1995. Go to original source... Go to PubMed...
  8. Kassa J. and J. Vachek: A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned mice and rats. Toxicology 177: 179-185, 2002. Go to original source... Go to PubMed...
  9. Kassa J., J. Vachek, J. Bajgar, J. Fusek: A combination of pyridostigmine with anticholinergic drugs:_effective pharmacological pretreatment of soman-poisoned mice. ASA Newslett. 16: 1-3, 2001.
  10. Kuča K., J. Bielavský, J. Cabal, J. Kassa: Synthesis of a new reactivator of tabun inhibited acetylcholinesterase. Bioorg. Med. Chem Lett. 13: 3545-3547, 2003. Go to original source...
  11. Kuča K. and J. Patočka: Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium oximes. J. Enzyme Inhib. Med. Chem. 19: 39-43, 2004. Go to original source... Go to PubMed...
  12. Lundy P.M., A.S. Hansen., B.T. Hand, C.A.Boulet: Comparison of several oximes against poisoning by soman, tabun and GF. Toxicology 72: 99-105, 1992. Go to original source... Go to PubMed...
  13. Marrs T.C.: Organophosphate poisoning. Pharmacol. Ther. 58: 51-66, 1993. Go to original source... Go to PubMed...
  14. Ohtomi S., S. Takase, F. Kumagai: Sarin poisoning in Japan. A clinical experience in Japan Self Defense Force (JSDF) Central Hospital. Int. Rev. Arm. 69: 97-102, 1996.
  15. Roth Z., M. Josífko, V. Trčka: Statistické metody v experimentální medicíně. Státní zdravotnické nakladatelství, Praha 1962, pp. 405-413.
  16. Stefanidou M., S. Athanaselis, M. Velonakis, F. Pappas, A. Koutselinis: Occupational exposure to cholinesterase inhibiting pesticides: a Greek case. Int. J. Environ. Health Res. 13: 23-29, 2003. Go to original source... Go to PubMed...
  17. Tallarida R. and R. Murray: Manual of pharmacological calculation with computer programs. Springer Verlag, New York 1987, pp.145.
  18. Vachek J., J. Kassa, J. Fusek, J. Bajgar: Present possibilities of treatment of organophosphate poisoning. Sborník vědeckých prací VLA JEP Hradec Králové 116: 67, 1993.
  19. Wenger B., M.D. Quigley, M.A. Kokla: Seven-day pyridostigmine administration and thermoregulation during rest and exercise in dry heat. Aviat. Space Environ. Med. 64: 905-911, 1993.
  20. Worek F., G. Reiter, P. Eyer, L. Szinicz: Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates. Arch. Toxicol. 76: 523-529, 2002. Go to original source... Go to PubMed...