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- MeSH
- akrolein analogy a deriváty farmakologie škodlivé účinky MeSH
- chemické bojové látky * farmakologie škodlivé účinky MeSH
- chloracetáty chemie škodlivé účinky MeSH
- dráždivé látky * dějiny škodlivé účinky MeSH
- fosgen analogy a deriváty farmakologie škodlivé účinky MeSH
- lidé MeSH
- sloučeniny bromu chemie škodlivé účinky MeSH
- slzné plyny chemie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Dual Use Research of Concern (DURC) deals with the unintended consequences of research and development and is particularly acute in the area of drug development. The United States National Science Advisory Board for Biosecurity (NSABB) has defined DURC as "research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health, agriculture, plants, animals, the environment, or materiel” (1). One particular receptor antagonist and glycolate anticholinergic compound (BZ, QNB or 3-quinuclidinyl benzilate) was stockpiled by the United States as a non-lethal chemical weapon that incapacitates and severely degrades the capability of exposed individuals (2). Given time and medical treatment, combatants and non-combatants exposed to such incapacitating agents could recover without any long-term effects. The purpose of this review is to identify potential new and more potent incapacitating agents based on the structures of BZ or atropine using peer reviewed publications of new pharmaceutical agents. A number of peer reviewed studies have reported on compounds with effects observed at lower concentrations than or comparable to BZ suggesting that these compounds could also be developed as potential chemical incapacitating chemical warfare agents and represent good examples of the principal of Dual Use Research of Concern.
- MeSH
- antagonisté muskarinových receptorů * farmakologie chemická syntéza škodlivé účinky MeSH
- chemické bojové látky * farmakologie chemická syntéza škodlivé účinky MeSH
- chinuklidinylbenzilát * aplikace a dávkování farmakologie škodlivé účinky MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- lidé MeSH
- parasympatolytika MeSH
- receptory muskarinové účinky léků MeSH
- stereoizomerie MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Diagnosis of nerve agent intoxication is based on anamnestic data, clinical signs and laboratory examination. For acute poisoning, cholinesterase activity in the blood (erythrocyte AChE, plasma/serum BuChE) is sensitive, simple and most frequent laboratory examination performed in biochemical laboratories. Specialized examinations to precise treatment (reactivation test) or to make retrospective diagnosis (fluoride induced reactivation etc.) can be conducted. Other sophisticated methods are available, too.
- MeSH
- antidota farmakologie klasifikace MeSH
- atropin terapeutické užití MeSH
- autoaplikace přístrojové vybavení MeSH
- biologické bojové látky klasifikace normy MeSH
- centrální nervový systém metabolismus MeSH
- chemické bojové látky * farmakologie klasifikace normy toxicita MeSH
- cholinergní antagonisté farmakologie MeSH
- cholinesterasové inhibitory farmakologie klasifikace MeSH
- dioxiny toxicita MeSH
- fosgen analogy a deriváty toxicita MeSH
- fyziologie rostlin účinky léků MeSH
- halucinogeny MeSH
- herbicidy klasifikace MeSH
- hodnocení léčiv MeSH
- kyanovodík toxicita MeSH
- lidé MeSH
- LSD farmakologie klasifikace MeSH
- obidoxim chlorid MeSH
- organofosforové sloučeniny * farmakologie chemie klasifikace toxicita MeSH
- oxid uhelnatý toxicita MeSH
- příznaky a symptomy MeSH
- první pomoc * MeSH
- testy kožní dráždivosti MeSH
- yperit toxicita MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: Determination of acetylcholinesterase and butyrylcholinesterase activity has become an important tool in drug design and discovery as well as in medicine and toxicology. There are a large number of compounds that are able to modulate cholinesterase activity. These compounds can be used for pharmacological management of various disorders (e.g., Alzheimer's disease, myasthenia Gravis). Moreover, organophosphate poisoning is frequently diagnosed via a cholinesterase activity assay. This broad variety of methods has been developed over the past decades for cholinesterase activity quantification. AREAS COVERED: This review provides a summary of the methods that are based on specific properties of cholinesterases and their interactions with native or artificial substrates. The authors also aim to provide an overview of different techniques used for the determination of quantitative cholinesterase activity. Specifically, the authors describe and discuss the manometric, potentiometric, titrimetric, photometric, fluorometric, and radioisotopic methods. EXPERT OPINION: Existing methods are able to cover most of the problems that arise during cholinesterase activity determination. Colorimetry according to Ellman has proved to be the most useful and versatile approach. It may be used in various protocols for the determination of pesticide or nerve agent exposure or for the development of new drugs. Its possible improvement lies in optimization of hemoglobin-rich samples. The progress of the most common methods (including Ellman) depends on miniaturization and modern physical platforms (e.g., optical fibers, chip methods, or nanotechnologies).
- MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- butyrylcholinesterasa analýza metabolismus MeSH
- chemické bojové látky farmakologie MeSH
- chemické techniky analytické metody MeSH
- cholinesterasové inhibitory farmakologie MeSH
- cholinesterasy analýza metabolismus MeSH
- lidé MeSH
- myasthenia gravis farmakoterapie metabolismus MeSH
- racionální návrh léčiv MeSH
- referenční hodnoty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
A novel acetylcholinesterase (AChE) reactivator, a bispyridinium aldoxime named K048, was first synthesized in 2003. It is a promising antidote against tabun poisoning. Afterwards, other studies on several cholinesterases (ChE) of different species (humans, rats, etc.) and models (in vitro or in vivo) were conducted. We tested this oxime against nine different AChE inhibitors using in vitro tests on rat brain homogenate as source of enzyme. Our results showed that oxime K048 reached promising reactivation activity in case of all tested AChE inhibitors, except cyclosarin, at oxime concentration 10(-3) M. At a concentration of 10(-5) M, which is more common for human use, only methylchlorpyrifos-inhibited AChE was reactivated.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- aktivace enzymů účinky léků MeSH
- antidota farmakologie MeSH
- chemické bojové látky farmakologie MeSH
- cholinesterasové inhibitory farmakologie MeSH
- enzymové reaktivátory farmakologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- organofosforové sloučeniny farmakologie MeSH
- oximy farmakologie MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Reactivation with bis quaternary aldoxime HI-6, chemical formula 1-(2-hydroxyamino-methylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride of immobilized enzyme acetylcholinesterase inhibited by nerve agent type "G" was studied. This aldoxime is effective in reactivation of sarin-inhibited acetylcholinesterase. Substantially lower reactivation potency was observed with cyclosarin-inhibited enzyme and almost no effect was found for that acetylcholinesterase is the enzyme complex. HI 6 is completely ineffective towards the soman-inhibited enzyme: After a 2-minute inhibition of the enzyme with soman no ability to define reactivator the inhibited enzymes and complexes.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- biosenzitivní techniky MeSH
- chemické bojové látky farmakologie MeSH
- chemické modely MeSH
- cholinesterasové inhibitory farmakologie MeSH
- enzymy imobilizované MeSH
- indikátory a reagencie MeSH
- kinetika MeSH
- mozek enzymologie MeSH
- oximy MeSH
- prasata MeSH
- pyridinové sloučeniny MeSH
- reaktivátory cholinesterázy farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
