OP/nerve agents are still considered as important chemicals acting on living organisms and are widely used. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. Modeling of this action and extrapolation of experimental data from animals to humans is more possible for highly toxic agents than for the OP. The symptoms of intoxication comprise nicotinic, muscarinic, and central symptoms; for some OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases (AChE and BuChE) are characterized as the main enzymes involved in the toxic effect of these compounds, including molecular forms. The activity of both enzymes (and molecular forms) is influenced by inhibitors (reversible, irreversible, and allosteric) and other factors, such as pathological states. There are different methods for cholinesterase determination; however, the most frequent is the method based on the hydrolysis of thiocholine esters and subsequent detection of free SH-group of the released thiocholine. The diagnosis of OP/nerve agent poisoning is based on anamnesis, the clinical status of the intoxicated organism, and on cholinesterase determination in the blood. For nerve agent intoxication, AChE in the red blood cell is more diagnostically important than BuChE activity in the plasma. This enzyme is a good diagnostic marker for intoxication with OP pesticides. Some other biochemical examinations are recommended, especially arterial blood gas, blood pH, minerals, and some other specialized parameters usually not available in all clinical laboratories. These special examinations are important for prognosis of the intoxication, for effective treatment, and for retrospective analysis of the agent used for exposure. Some principles of prophylaxis against OP/nerve agent poisoning comprising the administration of reversible cholinesterase inhibitors such as pyridostigmine (alone or in combination with other drugs), scavengers such as preparations of cholinesterases, some therapeutic drugs, and possible combinations are given. Basic principles of the treatment of nerve agent OP poisoning are described. They are based on the administration of anticholinergics (mostly atropine but some other anticholinergics can be recommended) as a symptomatic treatment, cholinesterase reactivators as a causal treatment (different types but without a universal reactivator against all OP/nerve agents) as the first aid and medical treatment, and anticonvulsants, preferably diazepam though some other effective benzodiazepines are available. New drugs for the treatment are under experimental study based on new approaches to the mechanism of action. Future trends in the complex research of these compounds, which is important not only for the treatment of intoxication but also for the quantitative and qualitative increase of our knowledge of toxicology, neurochemistry, neuropharmacology, clinical biochemistry, and analytical chemistry in general, are characterized.

• MeSH
• lidé MeSH
• otrava organofosfáty * MeSH
• otrava diagnóza   farmakoterapie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Organophosphate (OP)-based pesticides and nerve agents are highly toxic compounds which interrupt the catalytic mechanism of acetylcholinesterase (AChE) by phosphorylating the hydroxyl moiety of serine residue. The inhibited enzyme can be reactivated by the nucleophilic action of oxime reactivators. To analyze the effect of different AChE sources on reactivation efficacy of reactivators, several in vivo studies have carried out using variety of AChE sources like pig, rat and monkey. Investigations on species differences provide a better insight for the development of new reactivators. Hence, present study was mainly targeted on comparative analysis of the reactivation of electric eel and human AChE inhibited by different OP. A series of butene-linked bis-pyridinium mono oximes which vary in functional groups present at the second pyridinium ring have been examined against sarin, VX, tabun and ethyl-paraoxon-poisoned AChE. In case of tabun-inhibited AChEs, tested oximes were better than reference oximes. For VX-poisoned human AChE, reactivator K251 (kr2;1.51 mM (-) (1 )min (-) (1)) showed good reactivation efficacy with standard oximes. Studies stipulated that butene-linked oximes consisting of different functional moieties are good reactivators and found to have better efficacy to reactivate nerve agent-inhibited human AChE in comparison to eel AChE.

• Klíčová slova
• Acetylcholinesterase, nerve agents, organophosphate, oxime, pesticides, reactivation,
• MeSH
• acetylcholinesterasa metabolismus   MeSH
• časové faktory MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• dospělí MeSH
• Electrophorus MeSH
• erytrocytární membrána účinky léků   enzymologie   MeSH
• kinetika MeSH
• lidé MeSH
• organofosfáty farmakologie   MeSH
• oximy farmakologie   MeSH
• reaktivátory cholinesterázy farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• organofosfáty MeSH
• oximy MeSH
• reaktivátory cholinesterázy MeSH

OBJECTIVES: Inhibition of the enzyme acetylcholinesterase (AChE) is the main mechanism both of therapeutic action of drugs for the treatment of Alzheimer's disease and toxic action of organophosphorus compounds. Various types of oximes reactivate AChE and are commonly used as antidotes against organophosphates (pesticides, nerve agents). METHODS: Effects both of AChE inhibitors (tacrine, 7-methoxytacrine) and oximes (pralidoxime, trimedoxime, obidoxime, methoxime, HI-6) on Complex I of electron transport chain (ETC) were examined. The enzyme activity was measured spectrophotometrically in crude mitochondrial fraction isolated from pig brain. RESULTS: Our results showed statistically significant Complex I inhibition by tacrine, other drugs did not affect the enzyme activity significantly. CONCLUSIONS: These observations suggest the possibility of tacrine-induced side effects related to disturbance in ETC. On the contrary, it seems that oximes do not affect cellular energetic metabolism.

• MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• elektronový transportní řetězec antagonisté a inhibitory   účinky léků   MeSH
• energetický metabolismus účinky léků   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• mozek - chemie účinky léků   MeSH
• oximy farmakologie   MeSH
• prasata MeSH
• reaktivátory cholinesterázy farmakologie   MeSH
• respirační komplex I metabolismus   MeSH
• takrin analogy a deriváty   farmakologie   MeSH
• techniky in vitro MeSH
• transport elektronů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7-methoxytacrine MeSH Prohlížeč
• cholinesterasové inhibitory MeSH
• elektronový transportní řetězec MeSH
• oximy MeSH
• reaktivátory cholinesterázy MeSH
• respirační komplex I MeSH
• takrin MeSH