Evaluation of medical countermeasures against organophosphorus compounds: the value of experimental data and computer simulations

Chemico-biological Interactions
Franz WorekHorst Thiermann

Abstract

Despite extensive research for more than six decades on medical countermeasures against poisoning by organophosphorus compounds (OP) the treatment options are meagre. The presently established acetylcholinesterase (AChE) reactivators (oximes), e.g. obidoxime and pralidoxime, are insufficient against a number of nerve agents and there is ongoing debate on the benefit of oxime treatment in human OP pesticide poisoning. Up to now, the therapeutic efficacy of oximes was mostly evaluated in animal models but substantial species differences prevent direct extrapolation of animal data to humans. Hence, it was considered essential to establish relevant experimental in vitro models for the investigation of oximes as antidotes and to develop computer models for the simulation of oxime efficacy in different scenarios of OP poisoning. Kinetic studies on the various interactions between erythrocyte AChE from various species, structurally different OP and different oximes provided a basis for the initial assessment of the ability of oximes to reactivate inhibited AChE. In the present study, in vitro enzyme-kinetic and pharmacokinetic data from a minipig model of dimethoate poisoning and oxime treatment were used to calculate dynamic changes ...Continue Reading

References

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May 21, 2005·Toxicology and Applied Pharmacology·Franz WorekHorst Thiermann
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Dec 25, 2007·BMC Public Health·David GunnellFlemming Konradsen
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Jan 29, 2010·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Harald JohnHorst Thiermann

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Citations

Jan 29, 2010·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Harald JohnHorst Thiermann
Mar 27, 2010·Chemico-biological Interactions·Patrick MassonOksana Lockridge
May 1, 2021·Biomolecules·Danna De BoerEric J Sorin

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