Alzheimer´s disease (AD) is a progressive neurodegenerative dementia which currently represents one of the
biggest threats for the human kind. The cure is still unknown and various hypotheses (cholinergic, amyloidal, oxidative,
vascular etc.) are investigated in order to understand the pathophysiology of the disease and on this basis find an effective
treatment. Tacrine, the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug,
however it was withdrawn from the market particularly due to its hepatotoxicity. Its derivative 7-methoxytacrine (7-
MEOTA) probably due to the different metabolization does not exert this side effect. The aim of our study was to compare
these two cholinesterase inhibitors from various, mainly cholinergic, points of view relevant for a potential AD drug.
We found that 7-MEOTA does not fall behind its more well-known parent compound – tacrine. Furthermore, we found,
that 7-MEOTA exerts better properties in most of the tests related to a possible AD treatment. Only the pharmacokinetics
and a higher acetylcholinesterase and butyrylcholinesterase inhibitory potency would slightly give advantages to tacrine
over 7-MEOTA, but concerning its lower toxicity, better antioxidant properties, interaction with muscarinic and nicotinic
receptors and “safer” metabolization provide strong evidence for reconsider 7-MEOTA and its derivatives as candidate
molecules for the treatment of AD.
Keywords: 7-Methoxytacrine, Acetylcholinesterase inhibitor, Alzheimer´s disease drug, Cholinergic hypothesis, Pharmacological
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