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Title: Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine

Abstract

Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 {mu}Mol paraoxon ({approx} LD{sub 75}) groups 2-6 received in addition: G{sub 2} 50 {mu}Mol tiapride 30 min before paraoxon; G{sub 3} 50 {mu}Mol tiapride 30 min before paraoxon and 50 {mu}Mol pralidoxime 1 min after paraoxon; G{sub 4} 1 {mu}Mol pyridostigmine 30 min before paraoxon; G{sub 5} 1 {mu}Mol pyridostigmine 30 min before paraoxon and 50 {mu}Mol pralidoxime 1 min after paraoxon; G{sub 6} 50 {mu}Mol pralidoxime 1 min after paraoxon; Mortality data were compared using Kaplan-Meier plots and logrankmore » tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G{sub 3}) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G{sub 5}). Tiapride pretreatment only (G{sub 2}) is inferior to pyridostigmine pretreatment only (G{sub 4}). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G{sub 4} and G{sub 6})« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [3]
  1. Department of Pharmacology and Therapeutics, FMHS UAE University (United Arab Emirates). E-mail: georg.petroianu@uaeu.ac.ae
  2. Department of Pharmacology and Therapeutics, FMHS UAE University (United Arab Emirates)
  3. Department of Community Medicine, FMHS UAE University (United Arab Emirates)
Publication Date:
OSTI Identifier:
20976890
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 219; Journal Issue: 2-3; Other Information: DOI: 10.1016/j.taap.2006.09.002; PII: S0041-008X(06)00304-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARBAMATES; CHOLINESTERASE; IN VITRO; MORTALITY; POISONING; RATS

Citation Formats

Petroianu, G.A., Hasan, M.Y., Nurulain, S.M., Arafat, K., Sheen, R., and Nagelkerke, N.. Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.09.002.
Petroianu, G.A., Hasan, M.Y., Nurulain, S.M., Arafat, K., Sheen, R., & Nagelkerke, N.. Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine. United States. doi:10.1016/j.taap.2006.09.002.
Petroianu, G.A., Hasan, M.Y., Nurulain, S.M., Arafat, K., Sheen, R., and Nagelkerke, N.. Thu . "Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine". United States. doi:10.1016/j.taap.2006.09.002.
@article{osti_20976890,
title = {Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: Tiapride vs. pyridostigmine},
author = {Petroianu, G.A. and Hasan, M.Y. and Nurulain, S.M. and Arafat, K. and Sheen, R. and Nagelkerke, N.},
abstractNote = {Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 {mu}Mol paraoxon ({approx} LD{sub 75}) groups 2-6 received in addition: G{sub 2} 50 {mu}Mol tiapride 30 min before paraoxon; G{sub 3} 50 {mu}Mol tiapride 30 min before paraoxon and 50 {mu}Mol pralidoxime 1 min after paraoxon; G{sub 4} 1 {mu}Mol pyridostigmine 30 min before paraoxon; G{sub 5} 1 {mu}Mol pyridostigmine 30 min before paraoxon and 50 {mu}Mol pralidoxime 1 min after paraoxon; G{sub 6} 50 {mu}Mol pralidoxime 1 min after paraoxon; Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G{sub 3}) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G{sub 5}). Tiapride pretreatment only (G{sub 2}) is inferior to pyridostigmine pretreatment only (G{sub 4}). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G{sub 4} and G{sub 6})},
doi = {10.1016/j.taap.2006.09.002},
journal = {Toxicology and Applied Pharmacology},
number = 2-3,
volume = 219,
place = {United States},
year = {Thu Mar 15 00:00:00 EDT 2007},
month = {Thu Mar 15 00:00:00 EDT 2007}
}