The value of novel oximes for treatment of poisoning by organophosphorus compounds

Poisoning by organophosphorus compounds (OP) still is a major therapeutic problem. Intentional OP pesticide poisoning results in up to 300.000 deaths each year and highly toxic OP nerve agents pose a permanent threat for the civilian population and military forces. The therapeutic value of clinically used oximes, pralidoxirne, obidoxime and TMB-4, in human OP pesticide poisoning is under debate. Moreover, these oximes lack efficacy in poisoning by various nerve agents. An innumerable number of novel oximes have been synthesized in the past five decades to provide more effective oximes and compounds with improved blood-brain-barrier penetration. Novel compounds were tested with largely different experimental protocols in vitro and in animals in vivo. The lack of comparable experimental conditions and the absence of human in vivo studies hamper a well-founded evaluation of the available data. At present, it appears that only a small number of (bispyridinium) oximes show superior potency and efficacy against individual OP. However, until now, no oxime with sufficient broad-spectrum activity against structurally different OP pesticides and nerve agents is available. An interim solution may be the combination of two oximes with overlapping reactivation spectrum. In conclusion, the unsatisfying situation calls for studies with standardized and comparable experimental conditions in order to allow a sound assessment of available and novel oximes. (C) 2013 Elsevier Inc. All rights reserved.