Irritants: a modern redefining of relevance to the armed forces and the prospect of creating medical means of protection

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Absract. Arguments are presented in favor of the increasing relevance of irritants to ensure the fulfillment of tasks by military personnel of the Armed Forces of the Russian Federation, as well as the need to reassess the risks to human health arising from their use. The results of an information-analytical data on methods and adverse effects of irritant application for purposes which are not prohibited by the «Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction» are presented. Modern ideas about molecular mechanisms of the effect of irritants on structures of the nervous system are considered, which are based on the fact that the provocative effect of irritants is realized by changing the permeability of cation channels of the transient receptor potential of type A1, expressed at the ends of sensitive neurons. The results of experimental and clinical studies of specific modulation of these channels using their natural and synthetic antagonists are analyzed. Structural formulas and basic pharmacological characteristics of the most active antagonists are given and the prospect of their use as a basis for the development of drugs for the treatment of irritant lesions is substantiated. The data on the use of solutions based on amphoteric and chelating agents for emergency treatment of skin areas infected with irritants is presented. A number of promising areas of research on the creation of effective medical means of protection against lesions by irritants has been identified.

Full Text

Restricted Access

About the authors

A. A. Kuzmin

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Author for correspondence.
Email: gniiivm_15@mil.ru
Russian Federation, Saint Petersburg

E. V. Ivchenko

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Email: gniiivm_15@mil.ru
Russian Federation, Saint Petersburg

A. B. Seleznev

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Email: gniiivm_15@mil.ru
Russian Federation, Saint Petersburg

S. P. Sidorov

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Email: gniiivm_15@mil.ru
Russian Federation, Saint Petersburg

M. A. Yudin

State scientific-research test Institute of military medicine of Defense Ministry of the Russian Federation

Email: gniiivm_15@mil.ru
Russian Federation, Saint Petersburg

References

  1. Ивченко, Е.В. Итоги и перспективы совершенствования средств и методов медицинской защиты от неблагориятных факторов химической природы / Е.В. Ивченко [и др.] // Воен.-мед. журн. – 2019. – Т. 340, № 9. – С. 14–21.
  2. Конвенция о запрещении разработки, производства, накопления и применения химического оружия и о его уничтожении / Сост. Ю.М. Колосов, Э.С. Кривчикова // Действующее международное право. – М.: МНИП, 1999. – Т. 2. – С. 441–447.
  3. Об утверждении Устава военной полиции Вооруженных Сил Российской Федерации и внесении изменений в некоторые акты Президента Российской Федерации. Указ Президента Российской Федерации от 25 марта 2015 г. № 161 // Собрание законодательства Российской Федерации. – 2015. – № 13. – Ст. 1909.
  4. Технология и стандартизация лекарств / Под ред. В.П. Георгиевского и Ф.А. Конева. – Харьков: РИРЕГ, 1996. – 784 с.
  5. Указания по военно-полевой терапии. – СПб.: Медиздат-СПб, 2019. – 464 с.
  6. Федеральный закон от 13 декабря 1996 г. № 150-ФЗ «Об оружии» // Собрание законодательства Российской Федерации. – 1996. – № 51. – Ст. 5681.
  7. Чепур, С.В. Перспективы развития военной токсикологии: химическая безопасность и противодействие ее угрозам / С.В. Чепур [и др.] // Воен.-мед. журн. – 2020. – Т. 341, № 1. – С. 57–63.
  8. Brône, B. Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor / B. Brône [et al.] // Toxicology and Applied Pharmacology. – 2008. – Vol. 238, Issue 2. – P. 150–156.
  9. Brotherton-Pleiss, C.E. Composes substitues du phenylcarbamate / C.E. Brotherton-Pleiss // Patent: WO2014/056958A1 17.04.2014, PCT/EP2013/070999.
  10. Brvar, M. Chlorobenzylidene malononitrile tear gas exposure: Rinsing with amphoteric, hypertonic, and chelating solution / M. Brvar // Hum. Exp. Toxicol. – 2016. – Vol. 35, Issue 2. – P. 213–218.
  11. Caceres, Ana I. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma / Ana I. Caceres [et al.] // PNAS. – 2009. – Vol. 106, Issue 22. – P. 9099–9104.
  12. Casarett & Doull’s Toxicology: The Basic Science Of Poisons / by C.D. Klaassen, M.O. Amdur, J. Doull. – 9th Edition // New York: McGraw-Hill, 2019. – 1639 p.
  13. Chung, K.F. Eight International London Cough Symposium 2014: Cough hypersensitivity syndrome as the basis for chronic cough / K.F. Chung, B. Canningc, L. McGarveyd // Pulm. Pharmacol. Ther. – 2015. – Vol. 35. – P. 76–80.
  14. DeFalco, J. Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor / Jeff DeFalco [et al.] // Bioorg. Med. Chem. Lett. – 2010. – Vol. 20, Issue 1. – P. 276–279.
  15. Everaerts, W. The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil / W. Everaerts [et al.] // Curr. Biol. – 2011. – Vol. 21, Issue 4. – P. 316–321.
  16. Fruttarolo, F. Novel sulfonamide trpa1 receptor antagonists / F. Fruttarolo [et al.] // Patent: WO2014/135617 12.09.2014, PCT/EP2014/054310.
  17. Gijsen, H.J.M. Tricyclic 3,4-dihydropyrimidine-2-thione derivatives as potent TRPA1 antagonists / Harrie J.M. Gijsen [et al.] // Bioorg. Med. Chem. Lett. – 2012. – Vol. 22, Issue 2. – P. 797–800.
  18. Giorgi, S. Is TRPA1 Burning Down TRPV1 as Druggable Target for the Treatment of Chronic Pain? / S. Giorgi [et al.] // Int. J. Mol. Sci. – 2019. – Vol. 20, Issue 12. – E. 2906.
  19. Gummin, D.D. 2017 Annual Report of the American Association of Poison Control Centers National Poison Data System (NPDS): 35th Annual Report / D.D. Gummin [et al.] // Clin. Toxicol. (Phila). – 2018. – Vol. 56, Issue 12. – P. 1213–1415.
  20. Jun, Ch. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation / Ch. Jun [et al.] // PAIN. – 2011. – Vol. 152, Issue 5. – P. 1165–1172.
  21. Jun, Ch. TRPA1 as a drug target – promise and challenges / Ch. Jun, D.H. Hackos // Naunyn-Schmiedeberg’s Arch. Pharmacol. – 2015. – Vol. 388, Issue 4. – P. 451–463.
  22. Kanju, P. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain / P. Kanju [et al.] // Sci. Rep. – 2016. – Vol. 6. – P. 26894.
  23. Laliberte, S. Discovery of a series of aryl-N-(3-(alkylamino)-5-(trifluoromethyl)phenyl) benzamides as TRPA1 antagonists / S. Laliberte [et al.] // Bioorg. Med. Chem. Lett. – 2014. – Vol. 24, Issue 14. – P. 3204–3206.
  24. Li, Q. Inhibiting the transient receptor potential a1 ion channel / Q. Li // Patent: WO2014/113671 24.07.2014, PCT/US2014/012049.
  25. McNamara, Colleen R. TRPA1 mediates formalin-induced pain / Colleen R McNamara [et al.] // PNAS. – 2007. – Vol. 104, Issue 33. – P. 13525–13530.
  26. Nyman, E. In vitro pharmacological characterization of a novel TRPA1 antagonist and proof of mechanism in a human dental pulp model / E. Nyman [et al.] // J Pain Res. – 2013. – Vol. 6. – P. 511–517.
  27. Pain Therapeutics: Current and Future Treatment Paradigms / edited by Chariotte Allerton // Cambridge: RSC Pablishing, 2014. – 411 p.
  28. Paulsen, C. Structure of the TRPA1 ion channel suggests regulatory mechanisms / C. Paulsen [et al.] // Nature. – 2015. – Vol. 520, Issue 7548. – P. 511–517.
  29. Rooney, L. Discovery, Optimization, and Biological Evaluation of 5-(2- (Trifluoromethyl)phenyl)indazoles as a Novel Class of Transient Receptor Potential A1 (TRPA1) Antagonists / L. Rooney [et al.] // J Med Chem. – 2014. – Vol. 57, Issue 12. – P. 5129–5140.
  30. Rothenberg, C. Tear gas: an epidemiological and mechanistic reassessment / C. Rothenberg [et al.] // Ann. N.Y. Acad. Sci. – 2016. – Vol. 1378, Issue 1. – P. 96–107.
  31. Schep, L.J. Riot control agents: the tear gases CN, CS and OC – a medical review / L.J. Schep, R.J. Slaughter, D.I. McBride // J. R. Army Med. Corps. – 2015. – Vol. 161, Issue 2.– P. 94–99.
  32. Stopyra, J.P. Baby Shampoo to Relieve the Discomfort of Tear Gas and Pepper Spray Exposure: A Randomized Controlled Trial / J.P. Stopyra [et al.] // The Western Journal of Emergency Medicine. – 2018. – Vol. 19, Issue 2. – P. 294–300.
  33. Tseng, W.C. TRPA1 ankyrine repeat six interacts with a small molecule inhibitor chemotype / W.C. Tseng [et al.] // PNAS. – 2018. – Vol. 115, Issue 48. – P. 12301–12306.
  34. Wang, S. Cardamonin, a Novel Antagonist of hTRPA1 Cation Channel, Reveals Therapeutic Mechanism of Pathological Pain / S. Wang // Molecules. – 2016. – Vol. 21, Issue 9. – E. 1145.
  35. Wei, H. Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals / H. Wei [et al.] // Anesthesiology. – 2009. – Vol. 111. – P. 147–154.

Supplementary files

Supplementary Files
Action
1. Fig. Synthetic antagonists of TRPA1 (description in text)

Download (124KB)

Statistics

Views

Abstract: 68

Dimensions

Article Metrics

Metrics Loading ...

PlumX


Copyright (c) 2020 Kuzmin A.A., Ivchenko E.V., Seleznev A.B., Sidorov S.P., Yudin M.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies