title: Acute effects of an insect repellent, N,N-diethyl-m-toluamide, on cholinesterase inhibition induced by pyridostigmine bromide in rats.
abstract: Acute lethal interactions have been previously described between a cholinesterase (ChE) inhibitor, pyridostigmine bromide (PB), and the insect repellent, N,N-diethyl-m-toluamide (DEET). The mechanism of toxic interaction between these agents is unknown. Alterations in membrane permeability caused by DEET could facilitate or enhance absorption, or alter the distribution of peripherally restricted PB, causing increased inhibition of ChE at a given dose. Studies were conducted to investigate PB-induced ChE inhibition in the presence of DEET. Rats received ip injections of PB (1, 2, or 3 mg/kg), DEET (200 mg/kg), or PB + DEET at doses that potentiated acute lethality. ChE activity was measured in heart, diaphragm, blood, whole brain, or specific brain areas using a modified spectrophotometric assay. DEET did not alter PB-induced inhibition of ChE activity in rat diaphragm, heart, or blood. Administration of DEET alone had no effect on ChE activity. PB alone did not inhibit ChE in whole brain, but PB (3 mg/kg) + DEET (200 mg/kg) caused significant inhibition of whole brain ChE activity to approximately 60% of controls. In specific brain areas, (cortex, cerebellum, medulla, hypothalamus, hippocampus, midbrain, and striatum) PB alone did not inhibit ChE activity. PB (3 mg/kg) + DEET (200 mg/kg) reduced ChE activity to approximately 65-75% of controls in each brain area, but those results were not statistically significant. In conclusion, DEET did not alter PB-induced inhibition of ChE activity in the periphery. While DEET may have facilitated the access of PB into the CNS at high doses, it is doubtful that the resulting minor reduction in ChE activity would have resulted in death. It is unlikely that the lethal interaction between PB and DEET is mediated through a cholinergic effect resulting from increased inhibition of ChE.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA. Leslie.Chaney@APG.AMEDD.ARMY.MIL
authors.forename: L A
authors.initials: LA
authors.lastname: Chaney
authors.forename: R W
authors.initials: RW
authors.lastname: Wineman
authors.forename: R W
authors.initials: RW
authors.lastname: Rockhold
authors.forename: A S
authors.initials: AS
authors.lastname: Hume
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D002802:Cholinesterases / Q000032:analysis; D003671:DEET / Q000633:toxicity*; D004347:Drug Interactions; D007302:Insect Repellents / Q000633:toxicity*; D008297:Male; D011729:Pyridostigmine Bromide / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D002800:Cholinesterase Inhibitors; D007302:Insect Repellents; D003671:DEET; D002802:Cholinesterases; D011729:Pyridostigmine Bromide