Combination of Memantine and 6-Chlorotacrine as Novel Multi-Target Compound against Alzheimer's Disease

Current Alzheimer Research
Martina KaniakovaMartin Horak

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly. It is characterized as a multi-factorial disorder with a prevalent genetic component. Due to the unknown etiology, current treatment based on acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate receptors (NMDAR) antagonist is effective only temporary. It seems that curative treatment will necessarily be complex due to the multifactorial nature of the disease. In this context, the so-called "multi-targeting" approach has been established. The aim of this study was to develop a multi-target-directed ligand (MTDL) combining the support for the cholinergic system by inhibition of AChE and at the same time ameliorating the burden caused by glutamate excitotoxicity mediated by the NMDAR receptors. We have applied common approaches of organic chemistry to prepare a hybrid of 6-chlorotacrine and memantine. Then, we investigated its blocking ability towards AChE and NMDRS in vitro, as well as its neuroprotective efficacy in vivo in the model of NMDA-induced lessions. We also studied cytotoxic potential of the compound and predicted the ability to cross the blood-brain barrier. A novel molecule formed by combination of 6-chlorotacrine and memantine p...Continue Reading

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Citations

Nov 16, 2019·Current Alzheimer Research·Ondrej Soukup, Jan Korabecny
Jul 30, 2020·Acta Neuropathologica·Arne IttnerLars M Ittner
Sep 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giambattista MarottaAnna Minarini
Sep 17, 2020·Molecular Neurobiology·Md Sahab UddinMohamed M Abdel-Daim
Sep 30, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiang ZengZhengzhi Wu

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