title: Antagonism of anticholinesterase (DFP) toxicity by donepezil plus scopolamine: a preliminary study.
abstract: Studies in animals exploring the antagonism of the cholinesterase inhibitors soman and sarin have shown that pretreatment with low doses of the centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic agent, scopolamine, is effective against their lethality and toxicity. The current study evaluated the effects of pretreatment with the oral anticholinesterase agent, donepezil (Aricept, 2.0 mg/kg), used to treat Alzheimer's disease, with and without scopolamine in decreasing the hypothermic, hypokinetic, and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor diisopropyl fluorophosphate (DFP, 1.0 mg/kg) in adult Flinders sensitive line (FSL) male rats. Donepezil alone and donepezil plus scopolamine (0.1 mg/kg) to a greater extent antagonized the decrease in temperature, hypoactivity, and induction of diarrhea due to DFP observed at 4 h after its administration. However, donepezil alone induced hypothermia at 1 and 2 h after treatment. Therefore, these preliminary findings are encouraging, but many additional studies are needed to establish the effectiveness of donepezil as a prophylactic agent against irreversible cholinesterase inhibition by DFP.
authors.affiliation: Department of Psychiatry, University of North Carolina, CB# 7175, Medical Research Building A, Chapel Hill, NC 27599-7175, USA. David_Janowsky@med.unc.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Janowsky
authors.forename: John M
authors.initials: JM
authors.lastname: Davis
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D003967:Diarrhea / Q000139:chemically induced / Q000523:psychology; D000077265:Donepezil; D004347:Drug Interactions; D007189:Indans / Q000494:pharmacology*; D007531:Isoflurophate / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000523:psychology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018727:Muscarinic Antagonists; D010880:Piperidines; D007531:Isoflurophate; D000077265:Donepezil; D012601:Scopolamine