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

The Korea Institute of Military Science and Technology (한국군사과학기술학회)
권호 표지
DOI QR코드

DOI QR Code

Antidotal and Neuroprotective Efficacies of a Prophylactic Patch against Sarin and Soman Poisonings in Guinea Pigs

신경작용제 사린 및 소만 중독에 대한 기니픽에서의 예방패치의 해독 및 뇌보호 효능

  • Song, Youngjo (The 4th Research and Development Institute, Agency for Defense Development)
  • 송영조 (국방과학연구소 제4기술연구본부)
  • Received : 2020.09.08
  • Accepted : 2021.01.22
  • Published : 2021.02.05
Download PDF
⟨ Previous Next ⟩

Abstract

This study was designed to evaluate the prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against sarin and soman using guinea pig. The median lethal dose values of two nerve agents were calculated by a probit analysis of deaths occurring within 24 h. In this study, the values of median lethal dose of sarin and soman were determined to be 33.0 and 26.7 ㎍/kg in guinea-pigs, respectively. The guinea pigs treated with a prophylactic patch(4×5 ㎠) for 24 h were 100 % protected against a challenge of 1.5 LD50. The combinational KMARK-1(atropine and 2-PAM) and prophylactic patch were more effective than a single KMARK-1, a combination of pyridostigmine and KMARK-1 significantly. Epileptiform seizures in the guinea pigs treated with the combinational antidotes led to neuropathological changes, in comparison with intact feature of brain of the animal treated with the patch.

Keywords

References

  1. JH McDonough, TM Shih, "Pharmacological Modulation of Soman Induced Seizures," Neuroscience & Behavior Review, Vol. 17, pp. 203-215, 1993. https://doi.org/10.1016/S0149-7634(05)80151-4
  2. TM Shih, TA Koviak, BR Capricio, "Anticonvulsants for Poisoning by the Organophosphorus Compound Soman: Pharmacological Mechanisms," Neuroscience & Behavior Review, Vol. 15, pp. 349-362, 1991. https://doi.org/10.1016/S0149-7634(05)80028-4
  3. DE Lenz, D Yeung, JR Smith, RE Sweeney, LA Lumley, DM Cerasoli, "Stoichiometric and Catalytic Scavengers as Protection against Nerve Agent Toxicity: A Mini Review," Toxicology, Vol. 233, pp. 31-39, 2007. https://doi.org/10.1016/j.tox.2006.11.066
  4. TM Shih, SM Cuniho, JH McDonough, "Control of Nerve Agent Induced Seizures is Critical for Neuroprotection and Survival," Toxicology and Applied Pharmacology, Vol. 188, pp. 69-80, 2003. https://doi.org/10.1016/S0041-008X(03)00019-X
  5. AL, Vrdoljak, M Calic, B Radic, S Berend, D Jun, K Kuca, Z Kovarik, "Pretreatment with Pyridium Oximes Improves Antidotal Therapy against Tabun Poisoning," Toxicology, Vol. 228, pp. 41-50, 2006. https://doi.org/10.1016/j.tox.2006.08.012
  6. T Myhrer, NH Nguyen, JM Andersen, P Aas, "Protection against Soman-Induced Seizures in Rat : Relationship Among Doses of Prophylactics, Soman, and Adjuncts," Toxicology and Applied Pharmacology, Vol 196, pp. 327-336, 2004. https://doi.org/10.1016/j.taap.2004.01.007
  7. KD Spradling, JF Dillman, "Toxicology of Chemical Warfare Nerve Agent," Advances in Molecular Toxicology, Vol. 5, pp. 111-144, 2011. https://doi.org/10.1016/B978-0-444-53864-2.00003-7
  8. Y Meshulam, R Davidovici, A Wengier, A Levy, "Prophylactic Transdermal Treatment with Physostigmine and Scopolamine against Soman Intoxication in Guinea-Pigs," Journal of Applied Toxicology, Vol. 15, pp. 263-266, 1995. https://doi.org/10.1002/jat.2550150406
  9. IH Philippens, BPC Melchers, B Oliver, PLB Bruijnzeel, "Scopolamine Augments the Efficacy of Physostigmine against Soman Poisoning in Guinea Pigs," Pharmacology Biochemical, Behavior, Vol. 65, pp. 175-182, 2000. https://doi.org/10.1016/S0091-3057(99)00171-9
  10. YB Kim, KC Cheon, GH Hur, TS Phi, SJ Choi, D Hong, JK Kang, "Effects of Combinational Prophylactics Composed of Physostigmineand Procyclidine on Soman-Induced Lethality, Seizures and Brain Injuries," Environmental Toxicology and Pharmacology, Vol. 11(1), pp. 15-21, 2002. https://doi.org/10.1016/S1382-6689(01)00096-5
  11. EK Choi, D Park, JM Yon, GH Hur, YC Ha, JH Che, J Kim, S Shin, JY Jang, SY Hwang, YH Seong, DJ Kim, JC Kim, YB Kim, "Protection by Sustained Release of Physostigmine and Procyclidine of Soman Poisoning in Rats," European Journal of Pharmacology. Vol. 505(1-3), pp. 83-91, 2004. https://doi.org/10.1016/j.ejphar.2004.10.034
  12. WS Kim, Y Cho, JC Kim, ZZ Huang, SH Park, EK Choi, S Shin, SY Nam, JK Kang, SY Hwang, YB Kim, "Protection by a Transdermal Patch Containing Physostigmine and Procyclidine of Soman Poisoningin Dogs," European Journal of Pharmacology, Vol. 525(1-3), pp. 135-142, 2005. https://doi.org/10.1016/j.ejphar.2005.09.052