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

Lovrić, Jasna and Berend, Suzana and Lucić Vrdoljak, Ana and Radić, Božica and Katalinić, Maja and Kovarik, Zrinka and Želježić, Davor and Kopjar, Nevenka and Rast, Slavko and Mesić, Milan (2011) A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning. Acta Biochimica Polonica, 58 (2). pp. 193-8. ISSN 0001-527X

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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 % LD(50) doses of the new oxime survived after administration of 10.0 or 16.0 LD(50) 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.

Item Type: Article
MeSH: Acetylcholinesterase ; Adult ; Animals ; Antidotes/pharmacology ; Atropine Derivatives/chemical synthesis ; Atropine Derivatives/pharmacology ; Cell Death/drug effects ; Cell Survival/drug effects ; Cholinesterase Inhibitors/poisoning ; Cholinesterase Reactivators/pharmacology ; Enzyme Assays ; Erythrocytes/drug effects ; Erythrocytes/enzymology ; Humans ; Lymphocytes/drug effects ; Male ; Mice ; Paraoxon/poisoning ; Phosphoric Acid Esters/poisoning ; Pralidoxime Compounds/chemical synthesis ; Pralidoxime Compounds/pharmacology ; Soman/poisoning
Departments: Katedra za medicinsku kemiju, biokemiju i kliničku kemiju
Depositing User: Marijan Šember
Status: Published
Lucić Vrdoljak, AnaUNSPECIFIED
Katalinić, MajaUNSPECIFIED
Kovarik, ZrinkaUNSPECIFIED
Želježić, DavorUNSPECIFIED
Kopjar, NevenkaUNSPECIFIED
Date: 2011
Date Deposited: 03 Nov 2011 11:29
Last Modified: 03 Nov 2011 11:29
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/1368

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