Pharmacological therapeutic appliance for acute poisoning by organophosphorous compounds of anticholinesterase action (review of literature)

  • Authors: M.L. Zinovieva, N.V. Kurdil, P.G. Zhminko, M.G. Prodanchuk, O.P. Kravchuk, M.V. Velychko
  • UDC: 615.9; 615.917; 615.279
  • DOI: 10.33273/2663-4570-2023-94-1-42-54
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M. Zinovieva, N. Kurdil, P. Zhminko, M. Prodanchuk, O. Kravchuk, M. Velychko


LI Medved’s Research Centre of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine


ABSTRACT. The current standards of treatment the acute OPC poisoning with anticholinesterase action remain insufficient, despite the significant number of researches in this area conducted in the world. One of the ways to solve this problem is to use a wider range of pathogenetically determined pharmacologic agents.

The Aim of the Research. To observe and summarize the published results of investigation the pharmacological therapeutic appliance for acute OPC poisoning at the stages of preclinical and early clinical evaluation.

Methods. System content analysis of literature data using the PubMed and Google Scholar databases.

Results and Conclusions. The investigation of pharmacological therapeutic appliance effectiveness for acute anticholinesterase OPC poisoning remains relevant when taking into account the complexity of the intoxication pathogenesis. The main lines of pharmacological agents’ research for the acute anticholinesterase OPC poisoning include the study of n-cholinoreceptor antagonists, benzodiazepine receptor agonists, NMDA-receptor antagonists, H1-histamine receptor antagonists, alpha-adrenergic receptor agonists, enzymatic antidote, antioxidants, agonists of beta-adrenergic blockers, and also magnesium sulfate, sodium bicarbonate, lipid emulsions. The investigations of clinically available therapeutic appliance continue both in animal experiments and at the clinical application stage. Such investigations are also important given the need for poisoning emergency care under conditions when specific therapies are missing or limited.

Keywords: organophosphorus compounds, acute poisoning, therapeutic appliance.



1. Balan GM. Prodanchuk NG. Bubalo NN. Babich VA. Kharchenko OA. Sostoyaniye i perspektivy antidotnoy terapii ostrykh otravleniy pestitsidami. Сучасні проблеми токсикології, харчової та хімічної безпеки. 2015; (1–2):67–76.

2. Marcus H, De Souza RJ. Risk Factors for Acute Pesticide Poisoning in Developing Countries: A Systematic Review. Global Health: Annual Review. 2020;1(5):4.

3. Kharchenko OA, Balan HM, Bubalo NM. Hostri otruiennia fosfororhanichnymy spolukamy: osnovni klinichni syndromy ta mekhanizmy yikh formuvannia (ohliad literatury ta dani vlasnykh doslidzhen). Suchasni problemy toksykolohii, kharchovoi ta khimichnoi bezpeky. 2014; 5(68): 14–28.

4. Zinovieva ML, Kurdil NV, Prodanchuk MH, Kravchuk OP, Zhminko PH. Suchasni aspekty rozrobky zasobiv bazovoi terapii ta profilaktyky hostrykh otruien fosfororhanichnymy spolukamy(ohliad literatury). Ukrainskyi zhurnal suchasnykh problem toksykolohii. 2021;2(91):91–103.

5. Dvir H, Silman I, Harel M, Rosenberry TL, Sussman JL. Acetylcholinesterase: from 3D structure to function. Chemico-biological interactions. 2010;187(1–3):10–22.

6. Petrov KA. Kharlamova AD. Nikolskiy EE. Kholinesterazy: vzglyad neyrofiziologa. Geny i kletki. 2014;9(3):160–7.

7. McDonough JH Jr, Shih TM. Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neuroscience & biobehavioral reviews. 1997;21(5): 559–79.

8. Zhuang Q, Young A, Callam CS, McElroy CA, Ekici ÖD, Yoder RJ, Hadad CM. Efforts towards treatments against aging of organophosphorus-inhibited acetylcholinesterase. Annals of the New York Academy of Sciences. 2016; 1374(1):94–104.

9. Costa LG. Current issues in organophosphate toxicology. Clinica chimica acta. 2006;366(1–2):1–3.

10. Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462–70.

11. Dhanarisi J, Shihana F, Harju K, Mohamed F, Verma V, Shahmy S, et al. A pilot clinical study of the neuromuscular blocker rocuronium to reduce the duration of ventilation after organophosphorus insecticide poisoning. Clin Toxicol (Phila). 2020;58(4):254–61. doi: 10.1080/15563650.2019. 1643467.

12. Kassa J, Timperley CM, Bird M, Williams RL, Green AC, Tattersall JEH. Evaluation of the Influence of Three Newly Developed Bispyridinium Anti-nicotinic Compounds (MB408, MB442, MB444) on the Efficacy of Antidotal Treatment of Nerve Agent Poisoning in Mice. Basic Clin Pharmacol Toxicol. 2018;122(4):429–35.

13. Mokhort MA, Bobkova LS, Kyrychok LM, Prytula TP, Seredynska NM. Prohnozuvannia likuvalno-zakhysnykh vlastyvostei ta toksychnosti oksymnykh i bezoksymnykh chetvertynnykh pirydynovykh spoluk. Suchasni problemy toksykolohii. 2002;2:79-83.

14. Bajgar J, Fusek J, Kuca K, Bartosova L, Jun D. Treatment of organophosphate intoxication using cholinesterase reactivators: facts and fiction. Mini Rev Med Chem. 2007;7(5):461-6.

15. McCarren HS, McDonough JH Jr. Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides. Ann N Y Acad Sci. 2016;1374(1):144–50.

16. Petrov VI. Piotrovskiy LB. Grigorev IA. Vozbuzhdayushchiye aminokisloty. Volgograd: izd. Volg. med. akad.; 1997. 1–176.

17. Deshpande SS, Smith CD, Filbert MG. Assessment of primary neuronal culture as a model for soman-induced neurotoxicity and effectiveness of memantine as a neuroprotective drug. Arch Toxicol. 1995;69(6):384–90.

18. Shih T, McDonough JH Jr, Koplovitz I. Anticonvulsants for soman-induced seizure activity. J Biomed Sci. 1999;6(2):86–96.

19. de Groot DM, Bierman EP, Bruijnzeel PL, Carpentier P, Kulig BM, Lallement G, et al. Beneficial effects of TCP on soman intoxication in guinea pigs: seizures, brain damage and learning behaviour. J Appl Toxicol. 2001;21(1):57–65.

20. Gordon RK, Nigam SV, Weitz JA, Dave JR, Doctor BP, Ved HS. The NMDA receptor ion channel: a site for binding of Huperzine A. J Appl Toxicol. 2001;21(1):47–51.

21. Hirbec H, Gaviria M, Vignon J. Gacyclidine: a new neuroprotective agent acting at the N-methyl-D-aspartate receptor. CNS Drug Rev. 2001;7(2):172-98.

22. Lallement G, Baubichon D, Clarencon D, Galonnier M, Peoc’h M, Carpentier P. Review of the value of gacyclidine (GK-11) as adjuvant medication to conventional treatments of organophosphate poisoning:Primate experiments mimicking various scenarios of military or terrorist attack by soman. Neurotoxicology 1999;20:675–84.

23. Orzechowski RF, Currie DS, Valancius CA. Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models. Eur J Pharmacol. 2005;506(3):257–64.

24. Bird SB, Gaspari RJ, Lee WJ, Dickson EW. Diphenhydramine as a protective agent in a rat model of acute, lethal organophosphate poisoning. Acad Emerg Med. 2002;9(12):1369–72.

25. Seredynska NM. Antydotna terapiia ta shliakhy netradytsiinoi farmakolohichnoi korektsii kardiotoksychnykh efektiv za dii fosfororhanichnykh spoluk. Medytsyna neotlozhnыkh sostoianyi. 2014;2:36–39.

26. Liu WF. A symptomatological assessment of organophosphate-induced lethality in mice: comparison of atropine and clonidine protection. Toxicol Lett. 1991;56(1–2): 19–32.

27. Perera PM, Jayamanna SF, Hettiarachchi R, Abeysinghe C, Karunatilake H, Dawson AH, et al. A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning. Trials. 2009;10:73.

28. Lenz DE, Yeung D, Smith JR, Sweeney RE, Lumley LA, Cerasoli DM. Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review. Toxicology. 2007;33(1–3):31–9.

29. Palikov VA, Palikova YA, Dyachenko IA. Study of protective properties of butyrylcholinesterase in acute anticholinesterase poisoning on BChE-KO and BALB/c mice. Research Results in Pharmacology. 2020;6:41.

30. Raushel FM. Bacterial detoxification of organophosphate nerve agents. Curr Opin Microbiol. 2002;5(3):288–95.

31. Sogorb MA, Vilanova E, Carrera V. Future applications of phosphotriesterases in the prophylaxis and treatment of organophosporus insecticide and nerve agent poisonings. Toxicol Lett. 2004;151(1):219–33.

32. Maxwell DM, Brecht KM. Carboxylesterase: specificity and spontaneous reactivation of an endogenous scavenger for organophosphorus compounds. J Appl Toxicol. 2001; 21(1):103–7.

33. Lockridge O. Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharmacol Ther. 2015;148:34–46.

34. Richard SA, Frank EA, D'Souza CJ. Correlation between Cholinesterase and Paraoxonase 1 Activities:Case Series of Pesticide Poisoning Subjects. Bioimpacts. 2013;3(3): 119–22.

35. Petroianu G, Toomes LM, Petroianu A, Bergler W, Rüfer R. Control of blood pressure, heart rate and haematocrit during high-dose intravenous paraoxon exposure in mini pigs. J Appl Toxicol. 1998;18(4):293–8.

36. Singh G, Avasthi G, Khurana D, Whig J, Mahajan R. Neurophysiological monitoring of pharmacological manipulation in acute organophosphate (OP) poisoning. The effects of pralidoxime, magnesium sulphate and pancuronium. Electroencephalogr Clin Neurophysiol. 1998;107(2): 140–8.

37. Pajoumand A, Shadnia S, Rezaie A, Abdi M, Abdollahi M. Benefits of magnesium sulfate in the management of acute human poisoning by organophosphorus insecticides. Hum Exp Toxicol. 2004;23(12):565–9.

38. Basher A, Rahman SH, Ghose A, Arif SM, Faiz MA, Dawson AH. Phase II study of magnesium sulfate in acute organophosphate pesticide poisoning. Clin Toxicol (Phila). 2013;51(1):35–40.

39. Jamshidi F, Yazdanbakhsh A, Jamalian M, Khademhosseini P, Ahmadi K, Sistani A, et al. Therapeutic Effect of Adding Magnesium Sulfate in Treatment of Organophosphorus Poisoning. Open Access Maced J Med Sci. 2018; 6(11): 2051–6.

40. Vanova N, Pejchal J, Herman D, Dlabkova A, Jun D. Oxidative stress in organophosphate poisoning: role of standard antidotal therapy. J Appl Toxicol. 2018;38(8): 1058–70.

41. Yadav P, Jadhav SE, Kumar V, Kaul KK, Pant SC, Flora SJ. Protective efficacy of 2-PAMCl, atropine and curcumin against dichlorvos induced toxicity in rats. Interdiscip Toxicol. 2012;5(1):1–8.

42. Chowdhury FR, Rahman MM, Ullah P, Ruhan AM, Bari MS, Alam MMJ, et al. Salbutamol in acute organophosphorus insecticide poisoning - a pilotdose-response phase II study. Clin Toxicol (Phila). 2018;56(9):820–7.

43. Balali-Mood M, Salimifar H, & Shariate M. Effects of sodium bicarbonate in human organophosphate poisoning. In Proceedings of the third international Chemical and Biological Medical treatment symposium, Spiez, Switzerland, May(2000);7–12.

44. Balali-Mood M, Ayati MH, Ali-Akbarian H. Effect of high doses of sodium bicarbonate in acute organophosphorous pesticide poisoning. Clin Toxicol (Phila). 2005;43(6): 571–4.

45. Stefanovic D, Antonijevic B, Bokonjic D, Stojiljkovic MP, Milovanovic ZA, Nedeljkovic M. Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos. Basic Clin Pharmacol Toxicol. 2006;98(2):173–80.

46. Shetab-Boushehri SV. Dual opposite actions of sodium bicarbonate in treatment of acute organophosphate poisoning. EXCLI J. 2019;18:677–8.

47. Cave G, Harvey M, Willers J, Uncles D, Meek T, Picard J, et al. LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry. J Med Toxicol. 2014;10(2):133–42.

48 . Chhabria BA, Bhalla A, Shafiq N, Kumar S, Dhibar DP, Sharma N. Lipid emulsion for acute organophosphate insecticide poisoning - a pilot observational safety study. Clin Toxicol (Phila). 2019;57(5):318–24.

49. Dunn C, Bird SB, Gaspari R. Intralipid fat emulsion decreases respiratory failure in a rat model of parathion exposure. Acad Emerg Med. 2012;19(5):504–9.

50. Mir SA, Rasool R. Reversal of cardiovascular toxicity in severe organophosphate poisoning with 20% Intralipid emulsion therapy: case report and review of literature. AsiaPac J Med Toxicol. 2014;3:169–72.

51. Ozsoy AZ, Nursal AF, Karsli MF, Uysal M, Alici O, Butun I, et al. Protective effect of intravenous lipid emulsion treatment on malathion-induced ovarian toxicity in female rats. Eur Rev Med Pharmacol Sci. 2016;20(11):2425–34.

52. Esen M, Uysal M. Protective effects of intravenous lipid emulsion on malathion-induced hepatotoxicity. Bratisl Lek Listy. 2018;119(6):373–8.


Стаття надійшла до редакції 09.12.2022

The article was received by the editors on December, 12th, 2022