title: Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates.
abstract: Carbamates are widely used for pest control and act primarily by inhibition of insect and mammalian acetylcholinesterase (AChE). Accidental or intentional uptake of carbamates may result in typical signs and symptoms of cholinergic overstimulation which cannot be discriminated from those of organophosphorus pesticide poisoning. There is an ongoing debate whether standard treatment with atropine and oximes should be recommended for human carbamate poisoning as well, since in vitro and in vivo animal data indicate a deleterious effect of oximes when used in combination with the N-methyl carbamate carbaryl. Therefore, we performed an in vitro kinetic study to investigate the effect of clinically used oximes on carbamoylation and decarbamoylation of human AChE. It became evident that pralidoxime and obidoxime in therapeutic concentrations aggravate the inhibition of AChE by carbaryl and propoxur, with obidoxime being substantially more potent compared to 2-PAM. However, obidoxime had no impact on the decarbamoylation kinetics. Hence, the administration of 2-PAM and especially of obidoxime to severely propoxur and carbaryl poisoned humans cannot be recommended.
authors: Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany. Electronic address: timowille@bundeswehr.org.
authors: Timo
authors: T
authors: Wille
authors: Lisa
authors: L
authors: Kaltenbach
authors: Horst
authors: H
authors: Thiermann
authors: Franz
authors: F
authors: Worek
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000737:chemistry / Q000506:poisoning*; D012721:Carbaryl / Q000506:poisoning; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000506:poisoning*; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D009768:Obidoxime Chloride / Q000378:metabolism / Q000494:pharmacology; D010091:Oximes / Q000378:metabolism* / Q000494:pharmacology*; D010575:Pesticides / Q000737:chemistry / Q000506:poisoning*; D011220:Pralidoxime Compounds / Q000378:metabolism / Q000494:pharmacology; D001074:Propoxur / Q000506:poisoning
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D010091:Oximes; D010575:Pesticides; D011220:Pralidoxime Compounds; D009768:Obidoxime Chloride; D001074:Propoxur; D000110:Acetylcholinesterase; C028797:pralidoxime; D012721:Carbaryl
keywords: Carbamate; Carbamoylation; Decarbamoylation; Human acetylcholinesterase; Kinetics; Oximes