AIMS: Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure. Comparing the protective efficacy of five such cholinesterase inhibitors (physostigmine, pyridostigmine, ranitidine, tacrine, or K-27), we observed best protection for the experimental oxime K-27. The present study was undertaken in order to determine if additional administration of K-27 immediately after OPC (paraoxon) exposure can improve the outcome. METHODS: Therapeutic efficacy was assessed in rats by determining the relative risk of death (RR) by Cox survival analysis over a period of 48 h. Animals that received only pretreatment and paraoxon were compared with those that had received pretreatment and paraoxon followed by K-27 immediately after paraoxon exposure. RESULTS: Best protection from paraoxon-induced mortality was observed after pretreatment with physostigmine (RR = 0.30) and K-27 (RR = 0.34). Both substances were significantly more efficacious than tacrine (RR = 0.67), ranitidine (RR = 0.72), and pyridostigmine (RR = 0.76), which were less efficacious but still significantly reduced the RR compared to the no-treatment group (paraoxon only). Additional administration of K-27 immediately after paraoxon exposure (posttreatment) did not further reduce mortality. Statistical analysis between pretreatment before paraoxon exposure alone and pretreatment plus K-27 posttreatment did not show any significant difference for any of the pretreatment regimens. CONCLUSIONS: Best outcome is achieved if physostigmine or K-27 are administered prophylactically before exposure to sublethal paraoxon dosages. Therapeutic outcome is not further improved by additional oxime therapy immediately thereafter.

Bio Science Department COMSATS Institute of Information Technology Bio Sciences Block CUI Park Road Tarlai Kalan Islamabad 45550 Pakistan

Department of Anatomy and Cellular Biology College of Medicine and Health Sciences Khalifa University P O Box 127788 Abu Dhabi UAE

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanského 62 26 500 03 Hradec Kralove Czech Republic

Department of Pharmacology and Therapeutics College of Medicine and Health Sciences UAE University Al Ain 15551 UAE

Department of Pharmacology College of Medicine and Health Sciences Khalifa University P O Box 127788 Abu Dhabi UAE

Herbert Wertheim College of Medicine Department of Cellular Biology and Pharmacology Florida International University University Park GL 495 11200 SW 8th St Miami FL 33199 USA

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Catalytic Hydrolysis of Paraoxon by Immobilized Copper(II) Complexes of 1,4,7-Triazacyclononane Derivatives

Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl

Safety and Efficacy of New Oximes to Reverse Low Dose Diethyl-Paraoxon-Induced Ventilatory Effects in Rats