303 results match your criteria tabun sarin


Release of protein-bound nerve agents by excess fluoride from whole blood: GC-MS/MS method development, validation, and application to a real-life denatured blood sample.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 15;1179:122693. Epub 2021 Apr 15.

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, D-80937 Munich, Germany. Electronic address:

In analogy to the fluoride-induced regeneration of butyrylcholinesterase (BChE) inhibited by nerve agents a method was developed and optimized for whole blood samples. Compared to the plasma method, regeneration grade was found to be higher for cyclosarin (GF), i-butylsarin from VR, and n-butylsarin from CVX, but lower for sarin (GB), fluorotabun from tabun (GA), and ethylsarin from VX. Regeneration grade of soman (GD) is the same for both matrices because it is released from serum albumin and not from cholinesterases. Read More

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Structural and Biochemical Insights into the Inhibition of Human Acetylcholinesterase by G-Series Nerve Agents and Subsequent Reactivation by HI-6.

Chem Res Toxicol 2021 Mar 4;34(3):804-816. Epub 2021 Feb 4.

United States Army Futures Command, Combat Capabilities Development Command, Chemical Biological Center, Chemcial Sciences Division, Agent Chemistry Branch, Aberdeen Proving Ground, Aberdeen, Maryland 21010-5424, United States.

The recent use of organophosphate nerve agents in Syria, Malaysia, Russia, and the United Kingdom has reinforced the potential threat of their intentional release. These agents act through their ability to inhibit human acetylcholinesterase (hAChE; E.C. Read More

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Molecular Modeling Studies on the Multistep Reactivation Process of Organophosphate-Inhibited Acetylcholinesterase and Butyrylcholinesterase.

Biomolecules 2021 01 27;11(2). Epub 2021 Jan 27.

Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.

Poisoning with organophosphorus compounds used as pesticides or misused as chemical weapons remains a serious threat to human health and life. Their toxic effects result from irreversible blockade of the enzymes acetylcholinesterase and butyrylcholinesterase, which causes overstimulation of the cholinergic system and often leads to serious injury or death. Treatment of organophosphorus poisoning involves, among other strategies, the administration of oxime compounds. Read More

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January 2021

A Thermophilic Bacterial Esterase for Scavenging Nerve Agents: A Kinetic, Biophysical and Structural Study.

Molecules 2021 Jan 27;26(3). Epub 2021 Jan 27.

Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France.

Organophosphorous nerve agents (OPNA) pose an actual and major threat for both military and civilians alike, as an upsurge in their use has been observed in the recent years. Currently available treatments mitigate the effect of the nerve agents, and could be vastly improved by means of scavengers of the nerve agents. Consequently, efforts have been made over the years into investigating enzymes, also known as bioscavengers, which have the potential either to trap or hydrolyze these toxic compounds. Read More

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January 2021

Counteracting poisoning with chemical warfare nerve agents.

Arh Hig Rada Toksikol 2020 Dec 31;71(4):266-284. Epub 2020 Dec 31.

Institute for Medical Research and Occupational Health, Zagreb, Croatia.

Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Prompt action is therefore critical to improve the chances of victim's survival and recovery. Read More

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December 2020

Improving Quantification of tabun, sarin, soman, cyclosarin, and sulfur mustard by focusing agents: A field portable gas chromatography-mass spectrometry study.

J Chromatogr A 2021 Jan 13;1636:461784. Epub 2020 Dec 13.

Hazardous Materials Research Center (HMRC), Battelle Columbus Laboratories, Battelle Memorial Institute, Columbus, OH, USA.

Commercial gas chromatograph-mass spectrometers, one of which being Inficon's HAPSITE® ER, have demonstrated chemical detection and identification of nerve agents (G-series) and blistering agents (mustard gas) in the field; however most analyses relies on self-contained or external calibration that inherently drifts over time. We describe an analytical approach that uses target-based thermal desorption standards, called focusing agents, to accurately calculate concentrations of chemical warfare agents that are analyzed by gas chromatograph-mass spectrometry. Here, we provide relative response factors of focusing agents (2-chloroethyl ethyl sulfide, diisopropyl fluorophosphate, diethyl methylphosphonate, diethyl malonate, methyl salicylate, and dichlorvos) that are used to quantify concentrations of tabun, sarin, soman, cyclosarin and sulfur mustard loaded on thermal desorption tubes (Tenax® TA). Read More

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January 2021

SAW Chemical Array Device Coated with Polymeric Sensing Materials for the Detection of Nerve Agents.

Sensors (Basel) 2020 Dec 8;20(24). Epub 2020 Dec 8.

Laboratory of Intelligent Devices and Thermal Control, Department of Mechanical Engineering, INHA University, inha-ro 100, Incheon 22212, Korea.

G nerve agents are colorless, odorless, and lethal chemical warfare agents (CWAs). The threat of CWAs, which cause critical damage to humans, continues to exist, e.g. Read More

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December 2020

Engineered Recombinant PON1-OPH Fusion Hybrids: Potentially Effective Catalytic Bioscavengers against Organophosphorus Nerve Agent Analogs.

J Microbiol Biotechnol 2021 Jan;31(1):144-153

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Republic of Korea.

Organophosphorus nerve agents (OPNAs), including both G- and V-type nerve agents such as sarin, soman, tabun and VX, are extremely neurotoxic organophosphorus compounds. Catalytic bioscavengers capable of hydrolyzing OPNAs are under development because of the low protective effects and adverse side effects of chemical antidotes to OPNA poisoning. However, these bioscavengers have certain limitations for practical application, including low catalytic activity and narrow specificity. Read More

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January 2021

Neurochemical and Neurobiological Weapons.

Authors:
James J Sejvar

Neurol Clin 2020 11 12;38(4):881-896. Epub 2020 Sep 12.

Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop H24-12, Atlanta, GA 30033, USA. Electronic address:

Nerve agents and neurobiological weapons are among the most devastating and lethal of weapons. Acetylcholinesterase inhibitors act by increasing the amount of acetylcholine in the neuromuscular junction, resulting in flaccid paralysis. Tabun, VX, soman, and sarin are the major agents in this category. Read More

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November 2020

Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures.

Neuropharmacology 2020 12 6;181:108298. Epub 2020 Sep 6.

Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20814, USA; Department of Psychiatry, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA. Electronic address:

Nerve agents are organophosphorus acetylcholinesterase inhibitors. Acute exposure to nerve agents can cause rapid death. In this review, we summarize the history of nerve agent development and use in warfare, the mechanisms by which these agents cause death or long-term brain damage, and the treatments for preventing death or long-term morbidity. Read More

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December 2020

Influence of experimental end point on the therapeutic efficacy of the antinicotinic compounds MB408, MB442 and MB444 in treating nerve agent poisoned mice - a comparison with oxime-based treatment.

Toxicol Mech Methods 2020 Nov 20;30(9):703-710. Epub 2020 Sep 20.

Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (DSTL), Salisbury, United Kingdom.

Therapeutic efficacy of antidotal treatment of acute poisoning by nerve agents is generally assessed by the evaluation of LD values of nerve agents over 24 h following poisoning without or with a single administration of antidotal treatment. In this study, LD values of four nerve agents (sarin, soman, tabun and cyclosarin) for non-treated and treated poisoning were evaluated in mice for two experimental end points - 6 h and 24 h. While the efficacy of atropine or oxime-based antidotal treatment was the same regardless of the experimental end point, the therapeutic efficacy of all three newly developed bispyridinium non-oxime compounds (MB408, MB442, and MB444) was mostly slightly higher at the 6 h end point compared to the 24 h end point, although the therapeutic efficacy of MB compounds was not superior to oxime-based antidotal treatment. Read More

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November 2020

Enantioseparation, in vitro testing, and structural characterization of triple-binding reactivators of organophosphate-inhibited cholinesterases.

Biochem J 2020 08;477(15):2771-2790

Biochemistry and Organic Analytical Chemistry Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10 000 Zagreb, Croatia.

The enantiomers of racemic 2-hydroxyimino-N-(azidophenylpropyl)acetamide-derived triple-binding oxime reactivators were separated, and tested for inhibition and reactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibited with tabun (GA), cyclosarin (GF), sarin (GB), and VX. Both enzymes showed the greatest affinity toward the methylimidazole derivative (III) of 2-hydroxyimino-N-(azidophenylpropyl)acetamide (I). The crystal structure was determined for the complex of oxime III within human BChE, confirming that all three binding groups interacted with active site residues. Read More

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In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase.

Molecules 2020 Jul 2;25(13). Epub 2020 Jul 2.

Bundeswehr Institute of Pharmacology and Toxicology, D-80937 Munich, Germany.

The implementation of the Chemical Weapons Convention (CWC) in 1997 was a milestone in the prohibition of chemical warfare agents (CWA). Yet, the repeated use of CWA underlines the ongoing threat to the population. Organophosphorus (OP) nerve agents still represent the most toxic CWA subgroup. Read More

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Binding of Organophosphorus Nerve Agents and Their Simulants to Metal Salts.

ACS Appl Mater Interfaces 2020 Jul 25;12(27):30941-30953. Epub 2020 Jun 25.

Department of Chemical and Biological Engineering, University of Wisconsin - Madison, Madison, Wisconsin 53706, United States.

Nerve agents (NAs) pose a great threat to society because they are easy to produce and are deadly in nature, which makes developing methods to detect, adsorb, and destroy them crucial. To enable the development of these methods, we report the use of first principles electronic structure calculations to understand the binding properties of NAs and NA simulants on metal salt surfaces. We report calculated Gibbs free binding energies () for four NAs (tabun (GA), sarin (GB), soman (GD), and venomous X (VX)) and five NA simulants (dimethyl methylphosphonate (DMMP), dimethyl chlorophosphate (DMCP), trimethyl phosphate (TMP), methyl dichlorophosphate (MDCP), and di-isopropyl methylphosphonate (DIMP)) on metal perchlorate and metal nitrate salts using density functional theory. Read More

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Synthesis and in vitro evaluation of novel non-oximes for the reactivation of nerve agent inhibited human acetylcholinesterase.

Chem Biol Interact 2020 Aug 23;326:109139. Epub 2020 May 23.

TNO, Lange Kleiweg 137, 2288, GJ Rijswijk, the Netherlands.

Since several decades oximes have been used as part of treatment of nerve agent intoxication with the aim to restore the biological function of the enzyme acetylcholinesterase after its covalent inhibition by organophosphorus compounds such as pesticides and nerve agents. Recent findings have illustrated that, besides oximes, certain Mannich phenols can reactivate the inhibited enzyme very effectively, and may therefore represent an attractive complementary class of reactivators. In this paper we further probe the effect of structural variation on the in vitro efficacy of Mannich phenol based reactivators. Read More

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Structural and Functional Characterization of New SsoPox Variant Points to the Dimer Interface as a Driver for the Increase in Promiscuous Paraoxonase Activity.

Int J Mol Sci 2020 Mar 1;21(5). Epub 2020 Mar 1.

Institute of Biochemistry and Cell Biology, CNR, 80131 Naples, Italy.

Increasing attention is more and more directed toward the thermostable Phosphotriesterase-Like-Lactonase (PLL) family of enzymes, for the efficient and reliable decontamination of toxic nerve agents. In the present study, the DNA Staggered Extension Process (StEP) technique was utilized to obtain new variants of PLL enzymes. Divergent homologous genes encoding PLL enzymes were utilized as templates for gene recombination and yielded a new variant of SsoPox from . Read More

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Gene therapy delivering a paraoxonase 1 variant offers long-term prophylactic protection against nerve agents in mice.

Sci Transl Med 2020 01;12(527)

Medical Toxicology Research Division, Biochemistry & Physiology Department, Agent Mitigation, United States Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, USA.

Chemical warfare nerve agents are organophosphorus chemical compounds that induce cholinergic crisis, leaving little or no time for medical intervention to prevent death. The current chemical treatment regimen may prevent death but does not prevent postexposure complications such as brain damage and permanent behavioral abnormalities. In the present study, we have demonstrated an adeno-associated virus 8 (AAV8)-mediated paraoxonase 1 variant IF-11 (PON1-IF11) gene therapy that offers asymptomatic prophylactic protection to mice against multiple lethal doses of G-type chemical warfare nerve agents, namely, tabun, sarin, cyclosarin, and soman, for up to 5 months in mice. Read More

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January 2020

Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure.

Rapid Commun Mass Spectrom 2020 May;34(9):e8721

State Key Laboratory of NBC Protection for Civilians, Beijing, 102205, China.

Rationale: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. Read More

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A Strip Biosensor with Guinea Green B and Fuchsin Basic Color Indicators on a Glass Nanofiber Carrier for the Cholinesterase Detection of Nerve Agents.

ACS Omega 2019 Dec 2;4(25):20978-20986. Epub 2019 Dec 2.

Oritest spol. s.r.o., Nábřežní 90/4, 150 00 Prague, Czech Republic.

This paper deals with the innovation of the Czech colorimetric biosensor Detehit designed for the simple, fast, and sensitive detection of nerve agents. The innovation is based on the use of an indicator consisting of a mixture of two triphenylmethane dyes, Guinea green B and a basic fuchsin, on a glass nanofiber filter paper carrier. The advantage of this solution is the blue-red color transition, which is much more visible than the white-yellow transition of other Detehit biosensors. Read More

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December 2019

Evaluation of high-affinity phenyltetrahydroisoquinoline aldoximes, linked through anti-triazoles, as reactivators of phosphylated cholinesterases.

Toxicol Lett 2020 Mar 19;321:83-89. Epub 2019 Dec 19.

Institute for Medical Research and Occupational Health, HR-10000 Zagreb, Croatia. Electronic address:

Acetylcholinesterase (AChE) is a pivotal enzyme in neurotransmission. Its inhibition leads to cholinergic crises and could ultimately result in death. A related enzyme, butyrylcholinesterase (BChE), may act in the CNS as a co-regulator in terminating nerve impulses and is a natural plasma scavenger upon exposure to organophosphate (OP) nerve agents that irreversibly inhibit both enzymes. Read More

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Protein adduct binding properties of tabun-subtype nerve agents after exposure in vitro and in vivo.

Toxicol Lett 2020 Mar 14;321:1-11. Epub 2019 Dec 14.

State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China. Electronic address:

Upon entering the body, nerve agents can bind active amino acid residues to form phosphonylated adducts. Tabun derivatives (O-alkyl-N,N-dialkyl phosphoroamidocyanidates) have strikingly different structural features from other G-series nerve agents, such as sarin and soman. Here, we investigate the binding mechanism for the phosphonylated adducts of nerve agents of tabun derivatives. Read More

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Unique coated neusilin pellets with a more distinct and fast visual detection of nerve agents and other cholinesterase inhibitors.

J Pharm Biomed Anal 2020 Feb 23;179:113004. Epub 2019 Nov 23.

Oritest Ltd., Nábřežní 90/4, Prague, Czech Republic; Faculty of Biomedical Engineering, Czech Technical University in Prague, Sítná 3105, Kladno, Czech Republic.

Pellets with an immobilized enzyme (acetyl- or butyrylcholinesterase) are the up-to-date type of carriers used for the detection of nerve agents (soman, sarin, tabun, VX, Novichok) and other cholinesterase inhibitors such as organophosphate and carbamate insecticides (parathion, malathion). They are used in the glass detection tubes as a layer containing the enzyme together with the second layer, which contains a colorimetric reagent and substrate. The detection method is based on the visually or spectrophotometrically observable Ellman's reaction, which develops a yellow color in the absence of the cholinesterase inhibitor; otherwise, the detector preserves its original color (preferably white). Read More

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February 2020

A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents.

Protein Eng Des Sel 2019 12;32(4):169-174

Department of Biomolecular Sciences, Weizmann Institute of Science, Herzl st. 234, Rehovot 7610001, Israel.

Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Read More

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December 2019

"Covalent-Assembly"-Based Fluorescent Probe for Detection of a Nerve-Agent Mimic (DCP) via Lossen Rearrangement.

Anal Chem 2019 09 15;91(17):10979-10983. Epub 2019 Aug 15.

Department of Chemistry and Chemical Engineering, School of Chemistry and Biological Engineering , University of Science and Technology Beijing , Beijing 100083 , China.

The highly selective and sensitive fluorescence "light-up" probe, 5'-(dimethylamino)-2'-formyl--hydroxy-[1,1'-biphenyl]-2-carboxamide(), has been fabricated for the nerve-agent mimic diethyl chlorophosphate (DCP). The probe is designed by combining two novel strategies of "covalent assembly" and Lossen rearrangement. Formation of a phosphoryl intermediate from DCP and a hydroxamic acid group in yields an isocyanate that quickly undergoes Lossen rearrangement to produce an aniline that condenses intramolecularly to a fluorescent phenanthridine system. Read More

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September 2019

Development of technologies applied to the biodegradation of warfare nerve agents: Theoretical evidence for asymmetric homogeneous catalysis.

Chem Biol Interact 2019 Aug 4;308:323-331. Epub 2019 Jun 4.

Laboratory of Molecular Modeling, Department of Chemistry, Federal University of Lavras, Lavras, MG, 37200-000, Brazil; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address:

Organophosphorus compounds have been widely employed to the development of warfare nerve agents and pesticides, resulting in a huge number of people intoxicated annually, being a serious problem of public health. Efforts worldwide have been done in order to design new technologies that are capable of combating or even reversing the poisoning caused by these OP nerve agents. In this line, the bioremediation arises as a promising and efficient alternative for this purpose. Read More

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Butyrylcholinesterase inhibited by nerve agents is efficiently reactivated with chlorinated pyridinium oximes.

Chem Biol Interact 2019 Jul 18;307:16-20. Epub 2019 Apr 18.

Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10000 Zagreb, Croatia. Electronic address:

Bispyridinium oximes with one (K865, K866, K867) or two (K868, K869, K870) ortho-positioned chlorine moiety, analogous to previously known K027, K048 and K203 oximes, and potent reactivators of human acetylcholinesterase (AChE) inhibited by nerve agents, were tested in the reactivation of human butyrylcholinesterase (BChE) inhibited by sarin, cyclosarin, VX, and tabun. A previously highlighted AChE reactivator, dichlorinated bispyridinium oxime with propyl linker (K868), was tested in more detail for reactivation of four nerve agent-BChE conjugates. Its BChE reactivation potency was showed to be promising when compared to the standard oximes used in medical practice, asoxime (HI-6) and pralidoxime (2-PAM), especially in case of sarin and tabun. Read More

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Acetylcholinesterase-functionalized two-dimensional photonic crystal for the sensing of G-series nerve agents.

Anal Bioanal Chem 2019 May 7;411(12):2577-2585. Epub 2019 Mar 7.

School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, China.

G-series nerve agents, such as sarin, tabun, and soman, would cause tremendous harm in military and terrorist attacks, so it is necessary to develop a simple method for the rapid and efficient detection of these hazardous substances. We have developed a tunable acetylcholinesterase (AChE)-functionalized two-dimensional photonic crystal (2D PhC) for the detection of a real nerve agent, sarin. In accordance with the 2D PhC previously prepared by our group, the AChE-functionalized 2D PhC was optimized by adjustment of the amount of monomer in the hydrogel, which not only increased the sensitivity of the 2D PhC, with the detection limit decreasing by two orders of magnitude, but also ensured the structural color spanned the whole visible region in the detection range. Read More

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Diagnoses of Pathological States Based on Acetylcholinesterase and Butyrylcholinesterase.

Authors:
Miroslav Pohanka

Curr Med Chem 2020 ;27(18):2994-3011

Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001 Hradec Kralove, Czech Republic.

Two cholinesterases exist: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). While AChE plays a crucial role in neurotransmissions, BChE has no specific function apart from the detoxification of some drugs and secondary metabolites from plants. Thus, both AChE and BChE can serve as biochemical markers of various pathologies. Read More

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Comparative effects of scopolamine and phencynonate on organophosphorus nerve agent-induced seizure activity, neuropathology and lethality.

Toxicol Mech Methods 2019 Jun 22;29(5):322-333. Epub 2019 Jan 22.

a Medical Toxicology Research Division , US Army Medical Research Institute of Chemical Defense , Edgewood , MD , USA.

The efficacy of anticonvulsant therapies to stop seizure activities following organophosphorus nerve agents (NAs) has been documented as being time-dependent. We utilized the guinea pig NA-seizure model to compare the effectiveness of phencynonate (PCH) and scopolamine (SCP) when given at the early (at time of seizure onset) or late (40 min after seizure onset) phase of seizure progression. PCH possesses both anticholinergic and anti-NMDA activities, while SCP is a purely anti-muscarinic compound. Read More

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