AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer's Disease

Molecular Pharmaceutics
Alexandre V IvachtchenkoYan A Ivanenkov

Abstract

Within the past decade several novel targets have been indicated as key players in Alzheimer-type dementia and associated conditions, including a "frightening" memory loss as well as severe cognitive impairments. These proteins are deeply implicated in crucial cell processes, e.g., autophagy, growth and progression, apoptosis, and metabolic equilibrium. Since recently, 5-HT6R has been considered as one of the most prominent biological targets in AD drug therapy. Therefore, we investigated the potential procognitive and neuroprotective effects of our novel selective 5-HT6R antagonist, AVN-211. During an extensive preclinical evaluation the lead compound demonstrated a relatively high therapeutic potential and improved selectivity toward 5-HT6R as compared to reference drug candidates. It was thoroughly examined in different in vivo behavioral models directly related to AD and showed evident improvements in cognition and learning. In many cases, the observed effect was considerably greater than that determined for the reported drugs and drug candidates, including memantine, SB-742457, and Lu AE58054, evaluated under the same conditions. In addition, AVN-211 showed a similar or better anxiolytic efficacy than fenobam, rufinamide, ...Continue Reading

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Citations

May 28, 2017·Journal of Alzheimer's Disease : JAD·Alexandre V IvachtchenkoAndrey Ivashchenko
Oct 18, 2019·Journal of Psychopharmacology·Helen Joan Cassaday, Karen Elizabeth Thur
May 8, 2018·Neurology and Therapy·Megan AndrewsMarwan N Sabbagh
Dec 18, 2020·European Journal of Medicinal Chemistry·Jakub StarońAndrzej J Bojarski
Feb 13, 2021·Journal of Experimental Pharmacology·Enrico CapuzziMassimiliano Buoli

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