title: New experimental Oximes in the management of organophosphorus pesticides poisoning.
abstract: Organophosphorus compounds (OPCs) are widely used in agriculture as pesticides and occasionally in industrial settings. They have also been developed as warfare nerve agents. OPCs poisoning from intentional, accidental, and occupational exposure is a major public health problem, especially across the rural developing world. The main toxic mechanism of OPCs is the inhibition of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), resulting in accumulation of acetylcholine (ACh) at the synapse with cholinergic crisis and possible death. Exposure to even small amounts of an OPC can be fatal and death is usually caused by respiratory failure. Standard treatment involves the administration of intravenous atropine and an oxime to counteract acetylcholinesterase inhibition at the synapse, but the usefulness of oximes is still debated. During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with OPCs. They act by reactivation of AChE inhibited by OPCs. However, their activity in poisonings with pesticides and warfare nerve agents is different, and there is still no universal oxime sufficiently effective against all known OPCs. The aim of this article was to review the most recent findings in this field and compare the protection conferred by the new K-oximes and sugar oximes with the effect of the four recommended pyridinium oximes (pralidoxime, obidoxime, trimedoxime, and HI-6), in the search for a broad-spectrum AChE reactivator.
authors.affiliation: Department of Anesthesiology and Intensive Care, Catholic University School of Medicine, Policlinico Universitario Agostino Gemelli, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Barelli
authors.forename: P M
authors.initials: PM
authors.lastname: Soave
authors.forename: M
authors.initials: M
authors.lastname: Del Vicario
authors.forename: R
authors.initials: R
authors.lastname: Barelli
mesh_terms: D000382:Agricultural Workers' Diseases / Q000139:chemically induced / Q000188:drug therapy; D016573:Agrochemicals / Q000506:poisoning; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use; D006801:Humans; D016273:Occupational Exposure; D062025:Organophosphate Poisoning; D010091:Oximes / Q000627:therapeutic use*; D010575:Pesticides / Q000506:poisoning*
chemical_list: D016573:Agrochemicals; D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D010575:Pesticides