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Usefulness of administration of non‐organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon
Author(s) -
Petroianu Georg A.,
Nurulain Syed M.,
Shafiullah Mohamed,
Hasan Mohamed Y.,
Kuča Kamil,
Lorke Dietrich E.
Publication year - 2013
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2760
Subject(s) - pyridostigmine , paraoxon , pharmacology , cholinesterase , acetylcholinesterase , pralidoxime , organophosphate , antidote , chemistry , medicine , toxicology , anesthesia , toxicity , enzyme , biochemistry , pesticide , biology , myasthenia gravis , agronomy
Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality‐reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon‐induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K‐27 (RR = 0.34); both treatments were significantly superior to the pre‐treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7‐MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon‐induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K‐27 is a promising alternative to pyridostigmine. Copyright © 2012 John Wiley & Sons, Ltd.