Reversible cholinesterase inhibitors as pre-treatment for exposure to organophosphates: assessment using azinphos-methyl
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...
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 2015
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| In: |
Journal of applied toxicology
Year: 2015, Volume: 35, Issue: 5, Pages: 493-499 |
| ISSN: | 1099-1263 |
| DOI: | 10.1002/jat.3052 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/jat.3052 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jat.3052 
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| Author Notes: | Georg A. Petroianu, Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuča and Dietrich E. Lorke |
| Summary: | 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. |
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| Item Description: | Gesehen am 11.12.2018 Published online in Wiley Online Library: 3 September 2014 |
| Physical Description: | Online Resource |
| ISSN: | 1099-1263 |
| DOI: | 10.1002/jat.3052 |