Reversible cholinesterase inhibitors as pre-treatment for exposure to organophosphates

• Verfasst von: Petroianu, Georg [VerfasserIn]
• Titel: Reversible cholinesterase inhibitors as pre-treatment for exposure to organophosphates
• Titelzusatz: assessment using azinphos-methyl
• Verf.angabe: Georg A. Petroianu, Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuča and Dietrich E. Lorke
• E-Jahr: 2015
• Jahr: May 2015
• Umfang: 7 S.
• Fussnoten: Gesehen am 11.12.2018 ; Published online in Wiley Online Library: 3 September 2014
• Titel Quelle: Enthalten in: Journal of applied toxicology
• Ort Quelle: Chichester [u.a.] : Wiley, 1981
• Jahr Quelle: 2015
• Band/Heft Quelle: 35(2015), 5, Seite 493-499
• ISSN Quelle: 1099-1263
• DOI: doi:10.1002/jat.3052
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: acetylcholine
• Sach-SW: azinphos-methyl
• Sach-SW: carbamates
• Sach-SW: cholinesterase
• Sach-SW: Cox analysis
• Sach-SW: organophosphate
• Sach-SW: oximes
• Sach-SW: prophylaxis
• Sach-SW: rat
• K10plus-PPN: 1585087602

Abstract

Pre-treatment with reversible acetylcholinesterase (AChE) inhibitors before organophosphorous compound (OPC) exposure can reduce OPC-induced mortality. However, pyridostigmine, the only substance employed for such prophylaxis, is merely efficacious against a limited number of OPCs. In search of more efficacious and broad-range alternatives, we have compared in vivo the ability of five reversible AChE inhibitors (pyridostigmine, physostigmine, ranitidine, tacrine and K-27) to reduce mortality induced by the OPC azinphos-methyl. Protection was quantified using Cox analysis by determining the relative risk (RR) of death in rats that were administered these AChE inhibitors in equitoxic dosage (25% of LD01) 30 min before azinphos-methyl exposure. Azinphos-methyl-induced mortality was significantly reduced by all five tested compounds as compared with the reference group that was only exposed to azinphos-methyl without prior pre-treatment (RR = 1). The most efficacious prophylactic agents were K-27 (RR = 0.15) and physostigmine (RR = 0.21), being significantly more efficacious than ranitidine (RR = 0.62) and pyridostigmine (RR = 0.37). Pre-treatment with tacrine (RR = 0.29) was significantly more efficacious than pre-treatment with ranitidine, but the difference between tacrine and pyridostigmine was not significant. Our results indicate that prophylactic administration of the oxime K-27 may be a promising alternative in cases of imminent OPC exposure.