한국군사과학기술학회지 (Journal of the Korea Institute of Military Science and Technology)

  • 제16권2호
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  • Pages.218-224
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  • 2013
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  • 1598-9127(pISSN)
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  • 2636-0640(eISSN)
한국군사과학기술학회 (The Korea Institute of Military Science and Technology)
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실험동물의 뇌파 측정에 의한 중추약물의 항경련효과 연구

A Study on the Anticonvulsant Effects of Centrally-Acting Drugs by Measuring Electroencephalography of Experimental Animals Intoxicated with Organophosphate Compounds

  • 투고 : 2013.02.08
  • 심사 : 2013.03.15
  • 발행 : 2013.04.05
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초록

Organophosphorus compounds are irreversible inhibitors of cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretion, tremor, convulsion, respiratory distress, epileptiform seizure, brain injuries and death. To protect brain injuries, administration of diazepam as a neuroprotectant is now considered essential for severely exposed nerve agent casualties. However, studies have shown diazepam to provide less than total protection against the neuropathological consequences of nerve agent exposure. In this context, extensive studies have been carried out to find out effective alternative drugs to protect brain from epileptiform seizures induced by organophosphate compounds intoxication. It has been reported that a combination of carbamate and anticholinergic or antiglutamatergic can be a very effective medical countermeasure in dealing with the threat of organophosphorous poisoning. In this study, experimental animals including rats and guinea pigs were implanted with microelectrodes on their brain sculls, and treated with various centrally acting drugs such as physostigmine and procyclidine prior to soman challenge, and then its electroencephalography(ECoG) was monitored to see anticonvulsant effects of the drugs. It was found that seizure activities in ECoG were not always in proportion to clinical signs induced by soman intoxication, and that combinative pretreatment with physostigmine plus procyclidine effectively stopped the seizures induced by organophosphorous poisoning.

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참고문헌

  1. McDonough, J. H., Jr., Shih, T. M., "Pharmacological Modulation of Soman-Induced Seizures", Neurosci. Biobehav. Rev., Vol. 17, pp. 203-215, 1993. https://doi.org/10.1016/S0149-7634(05)80151-4
  2. Shih, T. M., Koviak, T. A., Capricio, B. R., "Anti-Convulsants for Poisoning by the Organophosphorus Compound Soman : Pharmacological Mechanisms", Neurosci. Biobehav. Rev., Vol. 15, pp. 349-362. 1991. https://doi.org/10.1016/S0149-7634(05)80028-4
  3. Kim, Y.-B., Hur, G.-H., Shin, S., Sok, D.-E., Kang, J.-K., Lee Y.-S., "Organophosphate-Induced Brain Injuries : Delayed Apoptosis Mediated by Nitric Oxide", Environ. Toxicol. Pharmacol., Vol. 7, pp. 147-152, 1999. https://doi.org/10.1016/S1382-6689(99)00006-X
  4. McDonough, J. H., Jr., Jaax, N. K., Crowley, R. A., Mays, M. Z., Modrow, H. E., "Atropine and Diazepam Therapy Protects Against Soman-Induced Neural and Cardiac Pathology", Fund. Appl. Toxicol., Vol. 13, pp. 256-276, 1989. https://doi.org/10.1016/0272-0590(89)90262-5
  5. Tryphonas, L., Clement, J. G., "Histomorphogenesis of Soman-Induced Encephalocardiomyopathy in Sprague-Dawley Rats", Toxicol. Pathol., Vol. 23, pp. 393-409, 1995. https://doi.org/10.1177/019262339502300316
  6. Shih, T. M., Duniho, S. M., McDonough, J. H., "Control of Nerve Agent-Induced Seizures is Critical for Neuroprotection and Survival", Toxicol. Appl. Pharmacol., Vol. 188, pp. 69-80, 2003. https://doi.org/10.1016/S0041-008X(03)00019-X
  7. Spradling, K. D., Dillman, J. F., "Toxicology of Chemical Warfare Nerve Agents", Advances in Molecular Toxicology, Vol. 5, pp. 111-144, 2011. https://doi.org/10.1016/B978-0-444-53864-2.00003-7
  8. Myhrer, T., "Prophylactic and Therapeutic Measures in Nerve Agent Poisoning", Handbook of Toxicology of Chemical Warfare Agents, pp. 965-975, 2009.
  9. Joosen, M. J. A., Schans, M. J., Helden, H. P. M., "Efficacy of Combined Atropine, Obidoxime and Diazepam Treatment", Chem. Bio. Int., Vol. 188 (Issue 1, No. 6), pp. 255-263, 2010. https://doi.org/10.1016/j.cbi.2010.06.010
  10. Vrdoljak, A. L., Calic, M., Radic, B., Berend, S., Jun, D., Kuca, K., Kovarik, Z., "Pretreatment with Pyridium Oximes Improves Antidotal Therapy Against Tabun Poisoning", Toxicol. Vol. 228, pp. 41-50, 2006. https://doi.org/10.1016/j.tox.2006.08.012
  11. Kadar, T., Shapira, S., Cohen, G., Sahar, R., Alkalay, D., Raveh, L., "Sarin-Induced Neurophathology in Rats", Human Exp. Toxicol., Vol. 14, pp. 252-259, 1995. https://doi.org/10.1177/096032719501400304
  12. Philippens, I. H. C. H. M., Melchers, B. P. C., DeGroot, D. M. G., Wolthuis, O. I., "Behavioral Performance, Brain Histology and EEG Sequela After Immediate Combined Atropine/Diazepam Treatment of Soman-Intoxicated Rats", Pharmacol. Biochem. Behav., Vol. 42, pp. 711-719, 1992. https://doi.org/10.1016/0091-3057(92)90019-C
  13. McDonough, J. H., Jr., Dochterman, L. W., Smith, C. D., Shih, T. M., "Protection Against Nerve Agent-Induced Neuropathology, but Not Cardiac Pathology, is Associated with the Anticonvulsant Action of Drug Treatment", Neurotoxicology Vol. 15, pp. 123-132, 1995.
  14. Capacio, B. R., Whalley, C. E., Byers, C. E., McDonough, J. H., "Intramuscular Diazepam Pharmacokinetics in Soman-Exposed Guinea Pigs", J. Appl. Toxicol., Vol. 21, pp. S67-S74. 2001. https://doi.org/10.1002/jat.813
  15. LTS Lohmann Therapie-System AG(Germany), Prophylactic Transdermal Device Against Nerve Agents, White Paper, April, 2002.
  16. Kim, Y.-B., Cheon, K.-C., Hur, G.-H., Phi, T.-S., Choi, S.-J., Hong, D.-S., Kang, J.-K., "Effect of Combinational Prophylactics Composed of Physostigmine and Procyclidine on Soman-Induced Lethality, Seizures and Brain Injuries", Environ. Toxicol. Pharmacol., Vol. 11, pp. 15-21, 2002. https://doi.org/10.1016/S1382-6689(01)00096-5
  17. Kim, W.-S., Cho, Y., Kim, J.-C., Hang, Z.-Z., Park, S.-H., Choi, E.-K., Shin, S.-H., Nam, S.-Y., Kang, J.-K., Hwang, S.-Y., Kim, Y.-B., "Protection by a Transdermal Patch Containing Physostigmine and Procyclidine of Soman Poisoning In Dogs", Euro. J. Pharmacol., Vol. 21, pp. 135-142, 2005.
  18. Cho Y, Kim W-S, Hur G-H, Ha Y-C, "Minimum Effective Drug Concentrations of a Transdermal Patch System Containing Procyclidine and Physostigmine for Prophylaxis Against Soman Poisoning in Rhesus Monkeys", Environ. Toxicol. Pharmacol., Vol. 33, pp. 1-8, 2012. https://doi.org/10.1016/j.etap.2011.10.002