title: No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [123I]FP-CIT binding in rats.
abstract: OBJECTIVE
  [(123)I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [(123)I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [(123)I]FP-CIT.
  
  
  METHODS
  Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [(123)I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [(123)I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [(123)I]FP-CIT binding to DATs.
  
  
  RESULTS
  No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding.
  
  
  CONCLUSIONS
  We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [(123)I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of [(123)I]FP-CIT SPECT scans in routine clinical studies.
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 15 F2N, Amsterdam, The Netherlands. r.j.knol@amc.uva.nl
authors.forename: R J J
authors.initials: RJ
authors.lastname: Knol
authors.forename: K
authors.initials: K
authors.lastname: de Bruin
authors.forename: B L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.forename: J
authors.initials: J
authors.lastname: Booij
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D009662:Nortropanes / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002800:Cholinesterase Inhibitors; C097058:N-(2-fluoroethyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane; D009662:Nortropanes; D019275:Radiopharmaceuticals