Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD01 ) the prophylactic efficacy of five experimental (K-48, K-53, K-74, K-75, K-203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon. Mortalities were quantified by Cox analysis and compared with those observed after pretreatment with a strong acetylcholinesterase inhibitor (10-methylacridine) and after the FDA-approved pretreatment compound pyridostigmine. All nine tested substances statistically significantly reduced paraoxon-induced mortality. Best protection was conferred by the experimental oxime K-48, reducing the relative risk of death (RR) to 0.10, which was statistically significantly superior to pyridostigmine (RR = 0.31). The other oximes reduced the RR to 0.13 (obidoxime), 0.20 (K-203), 0.21 (K-74), 0.24 (K-75) and 0.26 (pralidoxime), which were significantly more efficacious than 10-methylacridine (RR = 0.65). These data support the hypothesis that protective efficacy is not primarily due to cholinesterase inhibition and indicate that the tested experimental oximes may be considered promising alternatives to the established pretreatment compound pyridostigmine.

College of Medicine and Health Sciences Department of Anatomy and Cellular Biology Khalifa University Abu Dhabi United Arab Emirates

Department of Bio Science COMSATS Institute of Information Technology Islamabad Pakistan

Department of Cellular Biology and Pharmacology Herbert Wertheim College of Medicine University Park GL 495 D Florida International University Miami Florida

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove Czech Republic

Department of Pharmacology and Therapeutics College of Medicine and Health Sciences UAE University United Arab Emirates

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

Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016-2019)