Medical Aspects of Chemical and Biological Warfare

Sidell, Frederick R.; Takafuji, Ernest T.; Franz, David R.

doi:10.21236/ada398241

Cited by 380 publications

(206 citation statements)

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“…[1][2][3][4][5][6][7][8][9][10][11] According to the World Health Organization, there are about 220,000 intoxications with organophosphorus pesticides throughout the world every year, leading to approximately 20,000 deaths. 1,[12][13][14] The most dangerous neurotoxic compounds are the chemical warfare agents soman (3), sarin (4), tabun (5) and VX (6) (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

The effect of neutral oximes on the reactivation of human acetylcholinesterase inhibited with paraoxon

Ribeiro¹,

Prates²,

Alves³

et al. 2012

J. Braz. Chem. Soc.

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Importantes agentes para defesa contra armas de guerra química são reativadores da acetilcolinesterase humana (huAChE) inibida por compostos organofosforados neurotóxicos (OP), e precisam de uma permeabilidade razoável pela barreira hematoencefálica (HB). Neste trabalho, oximas neutras, que penetram HB melhor do que as oximas catiônicas atualmente utilizadas como agentes de defesa, foram testadas como reativadores da huAChE inibida com paraoxon usando o método de Ellman modificado e pralidoxima (2-PAM) como padrão positivo. A oxima neutra mais ativa foi a 2-tiofenoaldoxima, que reativou 93% da huAChE inibida, sendo 12% mais eficiente do que a 2-PAM. Os resultados mostraram que oximas neutras simples possuem potencial para atuarem como antídotos para intoxicação com OPs neurotóxicos, sugerindo maior investigação no desenvolvimento de agentes de defesa neutros.Important defense agents against chemical warfare weapons, which are reactivators of human acetylcholinesterase (huAChE) inhibited by neurotoxic organophosphorus compounds (OP), need a reasonable permeation of the hematoencephalic barrier (HB). In this work, neutral oximes, which permeate HB better than the cationic oximes currently used as defense agents, were tested as reactivators of huAChE inhibited with paraoxon using the modified Ellman test with pralidoxime (2-PAM) as positive standard. The most active neutral oxime was (thiophen-2-yl)aldoxime, which reactivated 93% of the inhibited huAChE and was 12% more effective than 2-PAM. The results showed that simple neutral oximes have potential to function as antidotes for intoxication with neurotoxic OPs, suggesting further research on the development of neutral defense agents.Keywords: neutral oximes, huAChE reactivation, paraoxon, chemical warfare, (thiophen-2-yl)aldoxime IntroductionIntoxication with neurotoxic organophosphorus compounds is a serious problem caused by some pesticides used in agriculture, such as paraoxon (1) and malathion (2) ( Figure 1) and chemical warfare agents. [1][2][3][4][5][6][7][8][9][10][11] According to the World Health Organization, there are about 220,000 intoxications with organophosphorus pesticides throughout the world every year, leading to approximately 20,000 deaths. 1,[12][13][14] The most dangerous neurotoxic compounds are the chemical warfare agents soman (3), sarin (4), tabun (5) and VX (6) ( Figure 1). Though their use is prohibited by the United Nations, these agents have been employed as weapons by terrorist groups and by countries that did not sign the Chemical Weapon Convention administered by the Organization for the Prohibition of Chemical Weapons (OPCW).The principal target for the action of neurotoxic organophosphorus compounds is the enzyme acetylcholinesterase (AChE), a serine hydrolase that controls the nerve impulses at the cholinergic receptors in the central and peripheral nervous systems. 1,15-20 As shown in Ribeiro et al. 1217 Vol. 23, No. 7, 2012 Figure 2, the function of AChE (7) is the hydrolysis of the nerve impulse transmitter acetylcholine...

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Section: Introductionmentioning

confidence: 99%

The effect of neutral oximes on the reactivation of human acetylcholinesterase inhibited with paraoxon

Ribeiro¹,

Prates²,

Alves³

et al. 2012

J. Braz. Chem. Soc.

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“…5 Some of the main historical events involving CWAs in the 20 th century are listed in Table 1. 3,7 Although Japan used CWAs against the Chinese forces between the end of the 1930's and the beginning of the 1940's, it is interesting to note that there is no confirmation of the use of these weapons in Europe during World War II. This fact is astonishing, since Germany was much more advanced in that area than the Allies, to whom tabun, sarin and soman were completely unknown.…”

Section: History and Classification Of The Chemical War Agentsmentioning

confidence: 99%

“…10 As already discussed, tabun, sarin and soman were synthesized, but not employed, during World War II. VX was synthesized in Great Britain during the 1950's and later developed for military purposes by U.S.A. 3 Nerve agents are synthesized easily and cheaply, are easily dispersed and difficult to detect, feared by public opinion and highly lethal, being a excellent weapon for terrorist purposes. 13 Although there are several unconfirmed reports of nerve agents' utilization since 1967, 5 there are fortunately few confirmed cases of their use.…”

Section: -6mentioning

confidence: 99%

“…[1][2][3][4] Unfortunately, until now it has not been reported any oxime that acts efficiently against all the existing neurotoxic agents. Therefore, oximes that are efficient for the treatment of intoxication with one specific nerve agent can be completely ineffective with another.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, oximes that are efficient for the treatment of intoxication with one specific nerve agent can be completely ineffective with another. [1][2][3][4] Also, even the fast identification of a neurotoxic agent in order to choose the treatment for the intoxication is usually not rapid enough to either save the life of the patient or to avoid serious permanent damages.…”

Section: Introductionmentioning

confidence: 99%

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Organophosphorus compounds as chemical warfare agents: a review

Delfino¹,

Ribeiro²,

Figueroa‐Villar³

2009

J. Braz. Chem. Soc.

233

178

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Os agentes de guerra química constituem uma das maiores ameaças do mundo moderno. Dentre estes, destacam-se os agentes neurotóxicos, em virtude de sua alta letalidade e periculosidade. Eles são compostos organofosforados que atuam pela inibição da enzima acetilcolinesterase, a qual é fundamental no processo de transmissão de impulsos nervosos. Existem várias formas de tratamento para a intoxicação por organofosforados, mas nenhuma delas é eficaz contra todos os agentes conhecidos ou contra todos os seus efeitos. Esta revisão tem como foco o uso de compostos organofosforados como agentes neurotóxicos de guerra química. Após uma breve introdução histórica, será feita uma discussão sobre as principais características estruturais e biológicas da acetilcolinesterase, seguida por uma revisão das propriedades dos compostos organofosforados e da sua aplicação como agentes de guerra química. Por fim, serão discutidas as formas de tratamento contra estes agentes, com ênfase nas oximas usadas para reativar a acetilcolinesterase inibida.Chemical warfare agents constitute one of the greatest threats in the modern world. Among them, the neurotoxic agents are of special interest due to their high lethality and danger. Neurotoxic agents are organophosphorus compounds that act by inhibiting the enzyme acetylcholinesterase, which is fundamental for the control of transmission of nervous impulses. There are several ways of treating intoxication by organophosphorus compounds, but none of them is efficient against all the known neurotoxic agents or against all of their effects. This review focus on the use of organophosphorus compounds as neurotoxic chemical warfare agents. After a brief historical introduction, it will be done a discussion about the structural and biological characteristics of acetylcholinesterase, followed by a review of the properties of organophosphorus compounds and their application as chemical warfare agents. Finally, the ways of treatment against intoxication with these agents will be discussed, with emphasis on the oximes used for reactivating the inhibited acetylcholinesterase.

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