NDLI: Pretreatment for acute exposure to diisopropylfluorophosphate: in vivo efficacy of various acetylcholinesterase inhibitors.

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Pretreatment for acute exposure to diisopropylfluorophosphate: in vivo efficacy of various acetylcholinesterase inhibitors.

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Pretreatment for acute exposure to diisopropylfluorophosphate: in vivo efficacy of various acetylcholinesterase inhibitors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lorke, Dietrich E. Hasan, Mohamed Y. Nurulain, Syed M. Shafiullah, Mohamed Kuca, Kamil Petroianu, Georg A.
Description	Country affiliation: United States Author Affiliation: Lorke DE ( Department of Anatomy, FMHS, UAE University, Al Ain, UAE)
Abstract	Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors before exposure to organophosphorus compounds (OPCs) can reduce OPC-induced mortality. Pyridostigmine is the only FDA-approved substance for such use. The AChE-inhibitory activity of known AChE inhibitors was quantified in vitro and their in vivo mortality-reducing efficacy was compared, when given prophylactically before the exposure to the OPC diisopropylfluorophosphate (DFP). The IC50 was measured in vitro for the known AChE inhibitors pyridostigmine, physostigmine, ranitidine, tiapride, tacrine, 7-methoxytacrine, amiloride, metoclopramide, methylene blue and the experimental oxime K-27. Their in vivo efficacy, when given as pretreatment, to protect rats from DFP-induced mortality was quantified by determining the relative risk of death (RR) by Cox analysis, with RR = 1 for animals given only DFP, but no pretreatment. Physostigmine was the strongest in vitro AChE-inhibitor (IC50 = 0.012 µ m), followed by 7-methoxytacrine, tacrine, pyridostigmine and methylene blue. Ranitidine (IC50 = 2.5 µ m), metoclopramide and amiloride were in the mid-range. Tiapride (IC50 = 256 µ m) and K-27 (IC50 = 414 µ m) only weakly inhibited RBC AChE activity. Best in vivo protection from DFP-induced mortality was achieved when physostigmine (RR = 0.02) or tacrine (RR = 0.05) was given before DFP exposure, which was significantly superior to the pretreatment with all other tested compounds, except K-27 (RR = 0.18). The mortality-reducing effect of pyridostigmine, ranitidine and 7-methoxytacrine was inferior, but still significant. Tiapride, methylene blue, metoclopramide and amiloride did not significantly improve DFP-induced mortality. K-27 may be a more efficacious alternative to pyridostigmine, when passage into the brain precludes administration of physostigmine or tacrine.
File Format	HTM / HTML
ISSN	0260437X
Issue Number	6
Volume Number	31
e-ISSN	10991263
Journal	Journal of Applied Toxicology
Language	English
Publisher	Wiley
Publisher Date	2011-08-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Cholinesterase Inhibitors Pharmacology Isoflurophate Toxicity Amiloride Animals Dose-response Relationship, Drug Erythrocytes Enzymology Female Humans Inhibitory Concentration 50 Male Methylene Blue Metoclopramide Oximes Physostigmine Proportional Hazards Models Pyridinium Compounds Pyridostigmine Bromide Ranitidine Rats Tacrine Analogs & Derivatives Tiapride Hydrochloride Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Toxicology

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