Acetylcholinesterase Inhibitors as Pretreatment Before Acute Exposure to Organophosphates: Assessment Using Methyl-Paraoxon

Title:Acetylcholinesterase Inhibitors as Pretreatment Before Acute Exposure to Organophosphates: Assessment Using Methyl-Paraoxon

Volume: 11 Issue: 8

Author(s): Dietrich E. Lorke, Mohamed Y. Hasan, Syed M. Nurulain, Mohamed Shafiullah, Kamil Kuca and Georg A. Petroianu

Affiliation:

Keywords: Carbamates, cholinesterase, Cox analysis, methyl-paraoxon, oximes, organophosphate, pretreatment, prophylaxis, rat, methyl-paraoxon-induced, Prophylactic administration.

Abstract: Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of organophosphorus compounds (OPCs). The usefulness of pyridostigmine, the only compound approved by the Food and Drug Administration (FDA) for such pretreatment, has been questioned. In search for more efficacious alternatives, we have examined in vivo the efficacy of a group of ten compounds with known anti-AChE activity (pyridostigmine, metoclopramide, tiapride, ranitidine, physostigmine, tacrine, amiloride, methylene blue, 7- methoxytacrine and K-27) to reduce mortality induced by the OPC methyl-paraoxon. AChE inhibitors were given intraperitoneally in equitoxic dosage (25% of LD01) 30 min before OPC exposure. Protection was quantified in rats by determining the relative risk of death (RR) by Cox analysis, with RR=1 for animals given only methyl-paraoxon, but no pretreatment.

Cite this article as:

E. Lorke Dietrich, Y. Hasan Mohamed, M. Nurulain Syed, Shafiullah Mohamed, Kuca Kamil and A. Petroianu Georg, Acetylcholinesterase Inhibitors as Pretreatment Before Acute Exposure to Organophosphates: Assessment Using Methyl-Paraoxon, CNS & Neurological Disorders - Drug Targets 2012; 11 (8) . https://dx.doi.org/10.2174/1871527311211080016