title: In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases.
abstract: The simultaneous use of the repellent DEET, pyridostigmine, and organophosphorus pesticides has been assumed as a potential cause for the Gulf War Illness and combinations have been tested in different animal models. However, human in vitro data on interactions of DEET with other compounds are scarce and provoked the present in vitro study scrutinizing the interactions of DEET, pyridostigmine and pesticides with human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE). DEET showed to be a weak and reversible inhibitor of hAChE and hBChE. The IC(50) of DEET was calculated to be 21.7mM DEET for hAChE and 3.2mM DEET for hBChE. The determination of the inhibition kinetics of pyridostigmine, malaoxon and chlorpyrifos oxon with hAChE in the presence of 5mM DEET resulted in a moderate reduction of the inhibition rate constant k(i). The decarbamoylation velocity of pyridostigmine-inhibited hAChE was not affected by DEET. In conclusion, the in vitro investigation of interactions between human cholinesterases, DEET, pyridostigmine, malaoxon and chlorpyrifos oxon showed a weak inhibition of hAChE and hBChE by DEET. The inhibitory potency of the tested cholinesterase inhibitors was not enhanced by DEET and it did not affect the regeneration velocity of pyridostigmine-inhibited AChE. Hence, this in vitro study does not give any evidence of a synergistic effect of the tested compounds on human cholinesterases.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Wille
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002091:Butyrylcholinesterase; D004390:Chlorpyrifos / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003671:DEET / Q000737:chemistry / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008294:Malathion / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000737:chemistry; D010575:Pesticides / Q000737:chemistry / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D010575:Pesticides; D003671:DEET; C100082:malaoxon; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D004390:Chlorpyrifos; D011729:Pyridostigmine Bromide; D008294:Malathion