title: Organophosphorus pesticide-induced butyrylcholinesterase inhibition and potentiation of succinylcholine toxicity in mice.
abstract: Succinylcholine is the most important rapid-acting depolarizing muscle relaxant during anesthesia. Its desirable short duration of action is controlled by butyrylcholinesterase, the detoxifying enzyme. There are two reported cases of prolonged paralysis from succinylcholine in patients poisoned with the organophosphorus insecticides parathion and chlorpyrifos. The present study examines the possibility that other organophosphorus and methylcarbamate pesticides might also prolong succinylcholine action by inhibiting butyrylcholinesterase using mice treated intraperitoneally as a model and relating inhibition of blood serum hydrolysis of butyrylthiocholine to potentiated toxicity (mouse mortality). The organophosphorus plant defoliant tribufos (4 h pretreatment, 160 mg/kg) and organophosphorus plant growth regulator ethephon (1 h pretreatment, 200 mg/kg) potentiate the toxicity of succinylcholine by seven- and fourfold, respectively. Some other pesticides or analogs are more potent sensitizers for succinylcholine toxicity with threshold levels of 0.5, 1.0, 1.7, 8, 10, and 67 mg/kg for phenyl saligenin cyclic phosphonate, profenofos, methamidophos, tribufos, chlorpyrifos, and ethephon, respectively. Enhanced mortality from succinylcholine is generally observed when serum butyrylcholinesterase is inhibited 55-94%. Mivacurium, a related nondepolarizing muscle relaxant also detoxified by butyrylcholinesterase, is likewise potentiated by at least threefold on 4 hour pretreatment with tribufos (25 mg/kg) or profenofos (10 mg/kg).
authors.affiliation: Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Sparks
authors.forename: G B
authors.initials: GB
authors.lastname: Quistad
authors.forename: J E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000818:Animals; D001241:Aspirin / Q000633:toxicity; D002091:Butyrylcholinesterase / Q000097:blood / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D007306:Insecticides / Q000494:pharmacology*; D007546:Isoquinolines / Q000633:toxicity; D051379:Mice; D000077590:Mivacurium; D009943:Organophosphorus Compounds; D013390:Succinylcholine / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D007546:Isoquinolines; D009943:Organophosphorus Compounds; D000077590:Mivacurium; D002091:Butyrylcholinesterase; D013390:Succinylcholine; D001241:Aspirin