Optimal pre-treatment for acute exposure to the organophosphate dicrotophos
Background: Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsa...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2017
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| In: |
Current pharmaceutical design
Year: 2017, Jahrgang: 23, Heft: 23, Pages: 3432-3439 |
| ISSN: | 1873-4286 |
| DOI: | 10.2174/1381612822666161027154303 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.2174/1381612822666161027154303 Verlag, Volltext: http://www.eurekaselect.com.ezproxy.medma.uni-heidelberg.de/146777/article 
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| Verfasserangaben: | Dietrich E. Lorke, Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuča and Georg A. Petroianu |
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| 520 | |a Background: Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsatisfactory. Methods: In search of a better prophylactic compound, we determined in vivo the protection conferred by five cholinesterase inhibitors (ranitidine, physostigmine, tacrine, K-27 and pyridostigmine), which were administered in equitoxic dosage (1/4 of LD01) 30 minutes before exposure to the organophosphate dicrotophos. Efficacy was measured in rats by Cox analysis calculating the relative risk of death (RR), RR being 1 for the reference group which received dicrotophos and no prophylaxis. Results: K-27 (RR=0.06), physostigmine (RR=0.15), pyridostigmine (RR=0.22) and tacrine (RR=0.28) significantly (p ≤ 0.05) reduced dicrotophos-induced mortality in comparison to the reference group (dicrotophos without pre-treatment), whereas ranitidine (RR=0.86) had no significant influence. The experimental oxime K-27, when given before dicrotophos exposure, conferred the best in vivo protection. This was significantly (p ≤ 0.05) more efficacious than pre-treatment with any other tested compound. The differences in efficacy between the second best compound, physostigmine, and the less efficacious substances (tacrine and pyridostigmine) were also statistically significant. Conclusion: These data indicate that K-27 can be considered a very efficacious prophylactic agent for organophosphate exposure. | ||
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