Mechanism of organophosphates (nerve gases and pesticides) and antidotes: electron transfer and oxidative stress.
Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various physiological properties of iminium and oxime species are reviewed. The organophosphates encompass both nerve gases and insecticides, possessing similar properties, but different activities. Toxic manifestations are apparently due, in part, to oxidative stress. Alkylation of DNA takes place which may lead to generation of reactive oxygen species. Structure-activity relationships are examined, including reduction potentials and the captodative effect.
Kovacic
Peter
P
Department of Chemistry, San Diego State University, San Diego, CA 92182-0130, USA. pkovacic@sundown.sdsu.edu
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D009943:Organophosphorus Compounds; D018384:Oxidative Stress / Q000187:drug effects*; D011220:Pralidoxime Compounds / Q000494:pharmacology
D000931:Antidotes; D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D007306:Insecticides; D009943:Organophosphorus Compounds; D011220:Pralidoxime Compounds; C028797:pralidoxime