Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

Journal of Applied Toxicology : JAT
Victor A VoicuDalia Simona Miron

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 imp...Continue Reading

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Citations

Jan 15, 2013·Archives of Toxicology·Teresa R SternerJeffery M Gearhart
Nov 28, 2012·Expert Opinion on Drug Metabolism & Toxicology·Victor VoicuAndrei Medvedovici
Jan 12, 2016·Arhiv za higijenu rada i toksikologiju·Maja KatalinićZrinka Kovarik
Jan 5, 2011·Toxicology Letters·Zdeněk FišarKamil Kuča
Dec 15, 2010·Journal of Pharmaceutical and Biomedical Analysis·Jana Zdarova KarasovaKamil Kuca
May 5, 2016·Expert Opinion on Drug Metabolism & Toxicology·Victor A VoicuDalia Simona Miron
Jan 1, 2013·Acta Medica (Hradec Králové)·Jirí Bajgar
Jun 24, 2017·Chemical Reviews·Dominik K Kölmel, Eric T Kool

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