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the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug, however it was withdrawn from the market particularly due to its hepatotoxicity.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.

Biomedical Research Center University Hospital Hradec Kralove Sokolska 581 50005; Hradec Kralove Czech Republic

Citace poskytuje Crossref.org

The Effect of Tacrine on Functional Response of the Lower Oesophageal Sphincter Assessed by Endoscopic Luminal Impedance Planimetry in Experimental Pigs

Structure-Guided Design of N-Methylpropargylamino-Quinazoline Derivatives as Multipotent Agents for the Treatment of Alzheimer's Disease

Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities

Sustainable Drug Discovery of Multi-Target-Directed Ligands for Alzheimer's Disease

Effects of Novel Tacrine Derivatives on Mitochondrial Energy Metabolism and Monoamine Oxidase Activity-In Vitro Study

Pursuing the Complexity of Alzheimer's Disease: Discovery of Fluoren-9-Amines as Selective Butyrylcholinesterase Inhibitors and N-Methyl-d-Aspartate Receptor Antagonists

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

Exploring Structure-Activity Relationship in Tacrine-Squaramide Derivatives as Potent Cholinesterase Inhibitors

Technological Solutions for Older People with Alzheimer's Disease: Review

Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment

In Vitro Effects of Cognitives and Nootropics on Mitochondrial Respiration and Monoamine Oxidase Activity

Development of 2-Methoxyhuprine as Novel Lead for Alzheimer's Disease Therapy

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer's Agents: Design, Synthesis and Biological Evaluation

A 7-methoxytacrine-4-pyridinealdoxime hybrid as a novel prophylactic agent with reactivation properties in organophosphate intoxication

7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment

Alzheimer's disease and language impairments: social intervention and medical treatment