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Counteracting poisoning with chemical warfare nerve agents

Nikolina Maček Hrvat
Nikolina Maček Hrvat
 and 
Zrinka Kovarik
Zrinka Kovarik
   | Dec 31, 2020
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Article Category: Review
Published Online: Dec 31, 2020
Page range: 266 - 284
Received: Jul 01, 2020
Accepted: Nov 01, 2020
DOI: https://doi.org/10.2478/aiht-2020-71-3459
© 2020 Nikolina Maček Hrvat, Zrinka Kovarik, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Representatives of the G-series (tabun, sarin, soman, cyclosarin), V-series (VX, VR), IVA agents (GV), and Novichok series (16) of nerve agents (A-230, A-232, A234, A242, A-262)
Representatives of the G-series (tabun, sarin, soman, cyclosarin), V-series (VX, VR), IVA agents (GV), and Novichok series (16) of nerve agents (A-230, A-232, A234, A242, A-262)

Figure 2

Hydrolysis of acetylcholine (A), phosphylation and aging (B), and reactivation of nerve agent-inhibited acetylcholinesterase (C)
Hydrolysis of acetylcholine (A), phosphylation and aging (B), and reactivation of nerve agent-inhibited acetylcholinesterase (C)

Figure 3

Standard pyridinium aldoxime reactivators of phosphylated acetylcholinesterase, antimuscarinic atropine, and anticonvulsant diazepam, currently approved for nerve agent poisoning therapy
Standard pyridinium aldoxime reactivators of phosphylated acetylcholinesterase, antimuscarinic atropine, and anticonvulsant diazepam, currently approved for nerve agent poisoning therapy

Figure 4

Non-oxime compounds investigated as potential treatment in case of nerve agent poisoning (120, 123)
Non-oxime compounds investigated as potential treatment in case of nerve agent poisoning (120, 123)

Figure 5

Bioscavenging of native acetylcholinesterase from inhibition with nerve agents. A) stoichiometric bioscavenging; mole-to-mole reaction between exogenous enzyme scavenger and nerve agent, B) oxime-assisted catalytic scavenging; exogenous enzyme turned into catalytic bioscavenger in the presence of an oxime enabling nerve agent degradation by cycles of inhibition and reactivation of exogenous enzyme scavenger, C) catalytic bioscavenging; low amount of exogenous enzyme scavenger rapidly hydrolyses nerve agent with a turnover
Bioscavenging of native acetylcholinesterase from inhibition with nerve agents. A) stoichiometric bioscavenging; mole-to-mole reaction between exogenous enzyme scavenger and nerve agent, B) oxime-assisted catalytic scavenging; exogenous enzyme turned into catalytic bioscavenger in the presence of an oxime enabling nerve agent degradation by cycles of inhibition and reactivation of exogenous enzyme scavenger, C) catalytic bioscavenging; low amount of exogenous enzyme scavenger rapidly hydrolyses nerve agent with a turnover

Symptoms of nerve agent poisoning arising from acetylcholine build-up at muscarinic and nicotinic membrane receptors (8, 23, 40, 41)

System Symptoms
Brain Restlessness, headache, dizziness, convulsions, inhibition of central respiratory centres, loss of consciousness, coma
Eyes Blurred vision, conjunctivitis, myosis
Respiratory Rhinorrhoea, bronchoconstriction, bronchorrhea, pulmonary oedema
Cardiovascular Either tachycardia or bradycardia, and either hypotension or hypertension
Gastro-intestinal Cramping, abdominal pain, nausea, salivation, vomiting, defecation, urinary incontinence
Muscle Twitching, fasciculation, tremors, muscle cramps, paralysis
Skin Increased sweating
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