title: In vitro toxicity of rivastigmine and donepezil in cells of epithelial origin.
abstract: Neurospecific acetylcholinesterase inhibitors have been shown to lower intraocular pressure (IOP) in normal rabbits and might have additional neuroprotective effects. This study was set out to explore and compare the toxicity of two selective acetylcholinesterase inhibitors, rivastigmine and donepezil, on two standardized cell lines of epithelial origin. Chang and Vero cells were incubated with various concentrations of rivastigmine or donepezil. Acute toxicity (4 h) was assessed by monitoring the permeability of cells to propidium iodide. Chronic toxicity (7 days) was determined by monitoring the effect of the two drugs on esterase activity and cell proliferation. The viability of cells was also assessed morphologically by microscopic inspection. Signs of acute toxicity became manifest at a rivastigmine concentration of 50 mg/ml in both Chang and Vero cells. Indications of chronic toxicity became obvious at concentrations of as low as 1 x 10(-5) mg/ml. In contrast, degenerative morphological changes became manifest only at a concentration of as high as 1 mg/ml. In donepezil-treated cells, acute toxicity was not observed in the concentration range tested, whereas chronic toxicity was detected at 1 x 10(-1) mg/ml in both Chang and Vero cells, a concentration at which degenerative morphological changes became evident as well. In contrast to rivastigmine, donepezil elicited no signs of acute or chronic toxicity in either Chang or Vero cells at the IOP-lowering concentration of 1 x 10(-4) mg/ml. At this dose, the drug is therefore unlikely to evoke deleterious effects on ocular surface tissues in the clinical setting.
authors.affiliation: Department of Ophthalmology, University of Bern, Bern, Switzerland. goldblum@vsao.ch
authors.forename: David
authors.initials: D
authors.lastname: Goldblum
authors.forename: Monika
authors.initials: M
authors.lastname: Gygax
authors.forename: Mattias
authors.initials: M
authors.lastname: Böhnke
authors.forename: Justus G
authors.initials: JG
authors.lastname: Garweg
mesh_terms: D000818:Animals; D002219:Carbamates / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D000077265:Donepezil; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects*; D004950:Esterases / Q000378:metabolism; D006801:Humans; D007189:Indans / Q000633:toxicity*; D048448:Phenylcarbamates; D010880:Piperidines / Q000633:toxicity*; D011419:Propidium / Q000378:metabolism; D000068836:Rivastigmine; D014709:Vero Cells
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D011419:Propidium; D000077265:Donepezil; D004950:Esterases; D000068836:Rivastigmine