Knol_2008_Eur.J.Nucl.Med.Mol.Imaging_35_598

Reference

Title : No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [123I]FP-CIT binding in rats - Knol_2008_Eur.J.Nucl.Med.Mol.Imaging_35_598
Author(s) : Knol RJ , de Bruin K , van Eck-Smit BL , Booij J
Ref : Eur J Nucl Med Mol Imaging , 35 :598 , 2008
Abstract :

PURPOSE: [(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. CONCLUSION: 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.

PubMedSearch : Knol_2008_Eur.J.Nucl.Med.Mol.Imaging_35_598
PubMedID: 17955237

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Citations formats

Knol RJ, de Bruin K, van Eck-Smit BL, Booij J (2008)
No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [123I]FP-CIT binding in rats
Eur J Nucl Med Mol Imaging 35 :598

Knol RJ, de Bruin K, van Eck-Smit BL, Booij J (2008)
Eur J Nucl Med Mol Imaging 35 :598