Multi-target-directed therapeutic potential of 7-methoxytacrine-adamantylamine heterodimers in the Alzheimer's disease treatment

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• 作者：Zuzana Gazova^a ; ^{gazova@saske.sk} ; Ondrej Soukup^b ; ^c ; ^d ; Vendula Sepsova^b ; ^c ; Katarina Siposova^a ; Lucie Drtinova^c ; Petr Jost^b ; ^c ; Katarina Spilovska^b ; ^c ; ^d ; Jan Korabecny^b ; ^c ; ^d ; Eugenie Nepovimova^b ; ^c ; Diana Fedunova^a ; Martin Horak^e ; Martina Kaniakova^e ; Ze-Jun Wang^f ; Ayman K. Hamouda^f ; Kamil Kuca^b ; ^c ; ^d
• 关键词：Amyloid ; Aggregation ; Aβ peptide ; Muscarinic/nicotinic acetylcholine receptor antagonist ; N-Methyl-d-aspartate receptor antagonist ; β-Secretase inhibitor ; Alzheimer's disease
• 刊名：Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：1863
• 期：2
• 页码：607-619
• 全文大小：2200 K
• 卷排序：1863

文摘

Multitarget binding properties of 7-methoxytacrine - memantine heterodimers were tested. 7-methoxytacrine - memantine heterodimers inhibit Aβ peptide amyloid fibrillization. Heterodimers inhibit β-secretase activity depending on thiourea or urea linker length. Heterodimers act as antagonists for both M1 muscarinic and muscle-type nicotinic receptors. Heterodimers don't potentiate cholinergic transmission via the direct interaction with cholinergic receptors.