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• W2024784182 abstract "Abstract Undoubtedly, the use of oximes represents real progress in counteracting intoxications with organophosphates (OP), through potentiating antidotal effects of atropine. The penetration extent of these compounds through the blood–brain barrier (BBB) to significantly reactivate phosphorylated or phosphonylated acetylcholinesterase (AChE) in the brain still remains a debatable issue. Penetration of biological barriers by oximes was investigated mainly through determination of several quantitative parameters characterizing digestive absorption and BBB penetration. A weak penetration of biological barriers could be concluded from the available experimental data. The functional parameters/therapeutic effects following the penetration of oximes through BBB, more precisely the antagonism of OP‐induced seizures and hypothermia, prevention of brain damage and respiratory center protection, leading to the final end‐point, the survival of intoxicated organisms, are of high interest. It seems obvious that oximes are weakly penetrating the BBB, with minimal brain AChE reactivation (<5%) in important functional areas, such as the ponto‐medullar. The cerebral protection achieved through administration of oximes is only partial, without major impact on the antagonism of OP‐induced seizures, hypothermia and respiratory center inhibition. The antidotal effects probably result from synergic effects of other PD properties, different from the brain AChE reactivation process. Oxime structures especially designed for enhanced BBB penetration, through potentiating the hydrophobic characteristics, more often produce neurotoxic effects. Certainly, obtaining oximes with broad action spectrum (active against all OP types) would make a sense, but certainly, such a target is not achievable only through the increase in their penetrability in the brain." @default.
• W2024784182 created "2016-06-24" @default.
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• W2024784182 date "2010-11-01" @default.
• W2024784182 modified "2023-10-18" @default.
• W2024784182 title "Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review" @default.
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• W2024784182 doi "https://doi.org/10.1002/jat.1561" @default.
• W2024784182 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20635332" @default.
• W2024784182 hasPublicationYear "2010" @default.
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