Kinetics of brain cholinesterase inhibition following metrifonate administration

Shlomit Dachir, Bernard H. Schmidt, Aharon Levy

Research output: Contribution to journalArticlepeer-review

Abstract

In previous metrifonate (MTF) studies, there has been evidence for a preferential functional effect of the drug in cortical but not in striatal regions. In the present study we investigated the kinetics of brain cholinesterase (ChE) inhibition following an acute administration of MTF (100 mg/kg) in various brain regions of young and old Fischer 344 rats. The main objective was to test the hypothesis that the functional regional selectivity, observed in previous studies, was correlated with the extent of ChE inhibition. Using Karnovsky's method for histochemical staining, the highest staining intensity in control rats was found in the striatum and hippocampus, compared to a low basal activity in the frontal and frontoparietal cortices. In the striatum of drug treated old rats, enzyme inhibition was somewhat greater than that found in young rats. However, in the hippocampus, four to eight hours following MTF administration, the inhibition was greater in young compared to old rats. The differences in the sensitivity of various brain regions towards MTF induced ChE inhibition could not be correlated with the regional variation of MTF functional effects.

Original languageEnglish
Pages (from-to)1075-1080
Number of pages6
JournalNeurochemical Research
Volume24
Issue number8
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Alzheimer
  • Brain
  • Cholinesterase
  • Metrifonate
  • Rat

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