Optimal pre-treatment for acute exposure to the organophosphate dicrotophos

• Verfasst von: Lorke, Dietrich [VerfasserIn]
• Verfasst von: Petroianu, Georg [VerfasserIn]
• Titel: Optimal pre-treatment for acute exposure to the organophosphate dicrotophos
• Verf.angabe: Dietrich E. Lorke, Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuča and Georg A. Petroianu
• Jahr: 2017
• Umfang: 8 S.
• Fussnoten: Gesehen am 11.09.2018
• Titel Quelle: Enthalten in: Current pharmaceutical design
• Ort Quelle: Hilversum : Bentham Science Publ., 2000
• Jahr Quelle: 2017
• Band/Heft Quelle: 23(2017), 23, Seite 3432-3439
• ISSN Quelle: 1873-4286
• DOI: doi:10.2174/1381612822666161027154303
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580873006

Abstract

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.