Organophosphorus compounds (OP) are a constant problem, both in the military and in the civilian field, not only in the form of acute poisoning but also for their long-lasting consequences. No antidote has been found that satisfactorily protects against the toxic effects of organophosphates. Likewise, there is no universal cure to avert damage after poisoning. The key mechanism of organophosphate toxicity is the inhibition of acetylcholinesterase. The overstimulation of nicotinic or muscarinic receptors by accumulated acetylcholine on a synaptic cleft leads to activation of the glutamatergic system and the development of seizures. Further consequences include generation of reactive oxygen species (ROS), neuroinflammation, and the formation of various other neuropathologists. In this review, we present neuroprotection strategies which can slow down the secondary nerve cell damage and alleviate neurological and neuropsychiatric disturbance. In our opinion, there is no unequivocal approach to ensure neuroprotection, however, sooner the neurotoxicity pathway is targeted, the better the results which can be expected. It seems crucial to target the key propagation pathways, i.e., to block cholinergic and, foremostly, glutamatergic cascades. Currently, the privileged approach oriented to stimulating GABAAR by benzodiazepines is of limited efficacy, so that antagonizing the hyperactivity of the glutamatergic system could provide an even more efficacious approach for terminating OP-induced seizures and protecting the brain from permanent damage. Encouraging results have been reported for tezampanel, an antagonist of GluK1 kainate and AMPA receptors, especially in combination with caramiphen, an anticholinergic and anti-glutamatergic agent. On the other hand, targeting ROS by antioxidants cannot or already developed neuroinflammation does not seem to be very productive as other processes are also involved.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory toxicita   MeSH
• lidé MeSH
• neurotoxické syndromy * etiologie   prevence a kontrola   MeSH
• neurozánětlivé nemoci MeSH
• organofosfáty MeSH
• otrava organofosfáty * farmakoterapie   prevence a kontrola   MeSH
• reaktivní formy kyslíku MeSH
• záchvaty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: The aim of this study is to inform about different techniques used to improve treatment of nerve agents intoxication at the Department of Toxicology. METHODS: Different methods are briefly mentioned and their importance for development of more effective reactivators is discussed. RESULTS: Basic characterization of nerve agents and therapeutic drugs is necessary after literature survey. Usage of different techniques and properties of various reactivators are studied and, on this basis, the most effective ones are tested in details and proposed for practical use. CONCLUSIONS: The results described in this study clearly demonstrate that for the development of new and more effective cholinesterase reactivators, a complex approach using different methodical attitudes is necessary.

• MeSH
• acetylcholinesterasa škodlivé účinky   toxicita   MeSH
• biochemie metody   MeSH
• chemické bojové látky otrava   MeSH
• cholinesterasové inhibitory škodlivé účinky   toxicita   MeSH
• experimenty na zvířatech MeSH
• histocytochemie metody   MeSH
• lidé MeSH
• nervový systém účinky léků   MeSH
• organofosforové sloučeniny toxicita   MeSH
• otrava organofosfáty * prevence a kontrola   MeSH
• reaktivátory cholinesterázy * farmakologie   terapeutické užití   MeSH
• výzkum * MeSH
• výzkumné techniky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• akademie a ústavy MeSH
• antidota * aplikace a dávkování   terapeutické užití   MeSH
• experimenty na zvířatech MeSH
• hemoperfuze metody   využití   MeSH
• krysa rodu rattus MeSH
• metabolismus účinky léků   MeSH
• otrava organofosfáty * diagnóza   etiologie   prevence a kontrola   MeSH
• peritoneální dialýza metody   využití   MeSH
• respirační insuficience terapie   MeSH
• resuscitační péče * metody   využití   MeSH
• statistika jako téma MeSH
• takrin analogy a deriváty   terapeutické užití   MeSH
• toxikologie metody   organizace a řízení   trendy   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH