A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning

• Authors: Jasna Lovrić , Suzana Berend , Ana Lucić Vrdoljak , Božica Radić , Maja Katalinić , Zrinka Kovarik , Davor Želježić , Nevenka Kopjar , Slavko Rast , Milan Mesić
• Languages of publication: EN

Abstracts

EN

A conjugate of pyridine-4-aldoxime and atropine (ATR-4-OX) was synthesized and its antidotal efficiency was tested in vitro on tabun- or paraoxon-inhibited acetylcholinesterase (AChE) of human erythrocytes as well as in vivo using soman-, tabun- or paraoxon-poisoned mice. Its genotoxic profile was assessed on human lymphocytes in vitro and was found acceptable for further research. ATR-4-OX showed very weak antidotal activity, inadequate for soman or tabun poisoning. Conversely, it was effective against paraoxon poisoning both in vitro and in vivo. All animals treated with 5 % or 25 % LD50 doses of the new oxime survived after administration of 10.0 or 16.0 LD50 doses of paraoxon, respectively. Based on the persistence of toxicity symptoms in mice, the atropine moiety had questionable effects in attenuating such symptoms. It appears that ATR-4-OX has a therapeutic effect related to the reactivation of phosphylated AChE, but not to receptor antagonization.

Keywords

EN

antidotal potential; atropine; genotoxicity; pyridine-4-aldoxime; organophosphates

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2011
• Volume: 58
• Issue: 2
• Pages: 193-198

Dates

published

2011

received

2010-09-23

revised

2011-05-12

accepted

2011-06-09

(unknown)

2011-06-13

Contributors

author

Jasna Lovrić

• University of Zagreb, School of Medicine, Zagreb, Croatia

author

Suzana Berend

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Ana Lucić Vrdoljak

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Božica Radić

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Maja Katalinić

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Zrinka Kovarik

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Davor Želježić

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Nevenka Kopjar

• Institute for Medical Research and Occupational Health, Zagreb, Croatia

author

Slavko Rast

• Galapagos Research Centre d.o.o., Zagreb, Croatia

author

Milan Mesić

• Galapagos Research Centre d.o.o., Zagreb, Croatia

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