Chemical update on the potential for serotonin 5-HT6 and 5-HT7 receptor agents in the treatment of Alzheimer's disease.

Despite the better understanding of the mechanisms underlying Alzheimer's Disease (AD) and launched clinical trials, no AD-modifying treatment based on a synthetic drug has been introduced for almost twenty years. The serotonin 5-HT6 and 5-HT7 receptors turned out to be promising biological targets for modulation of central nervous system dysfunctions including cognitive impairment. Within this paper, we evaluate the pharmacological potency of both, 5-HT6R and 5-HT7R, agents in search for novel AD treatment. An overview of chemical structures of the 5-HTRs ligands with simultaneous procognitive action which have undergone preclinical and clinical studies within the last 10 years has been performed.

• Publication year

  2021

• Venue

  Bioorganic & Medicinal Chemistry Letters

• Publication date

  2021-07-23

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.bmcl.2021.128275PMID 34311086
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• New approaches to symptomatic treatments for Alzheimer’s disease

  2021cited by this paper
• 5-HT6 receptor agonism facilitates emotional learning

  2015cited by this paper
• Vortioxetine (brintellix): a new serotonergic antidepressant.

  2015cited by this paper
• Latrepirdine for Alzheimer's disease.

  2015cited by this paper
• 5-HT6 receptors and Alzheimer's disease

  2013cited by this paper
• Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

  2013cited by this paper
• Treatment of Alzheimer disease.

  2011cited by this paper
• Alzheimer’s disease

  2009cited by this paper

• Advancements of Potential Mechanisms of Repetitive Transcranial Magnetic Stimulation for Refractory Insomnia

  2025cites this paper
• 5-HT7 Receptors: New Horizons in the Therapy of Neuropsychiatric and Neurodegenerative Diseases

  2025cites this paper
• Targeting Oligodendrocyte Dysfunction in Alzheimer’s Disease: a New Frontier for Drug Repurposing with Antihistamines and Serotonin Receptor Agonists

  2025cites this paper
• The first-in-class 1,3,5-triazine-derived dual 5-HT6R/FAAH modulators in search for potential drug against neurodegenerative diseases with cognitive impairment.

  2025cites this paper
• Repeated 5-HT6 receptor activation facilitates flexible behavior in C57BL/6J mice.

  2025cites this paper
• Serotonergic Regulation in Alzheimer’s Disease

  2025cites this paper
• Targeting the serotonergic system in the treatment of neurodegenerative diseases—emerging therapies and unmet challenges

  2025cites this paper
• Advancements in the treatment of Alzheimer's disease: a comprehensive review

  2025cites this paper
• Serotonergic Modulators in Alzheimer's Disease: A Hope in the Hopeless Condition

  2025cites this paper
• Discovery of new dual butyrylcholinesterase (BuChE) inhibitors and 5-HT7 receptor antagonists as compounds used to treat Alzheimer's disease symptoms.

  2025cites this paper
• First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT6 Agents with a Beneficial Neuroprotective Profile against Alzheimer’s Disease

  2024cites this paper
• Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles

  2024cites this paper
• Review on anti-alzheimer drug development: approaches, challenges and perspectives

  2024cites this paper
• Clearing the Fog: A Review of Antipsychotics for Parkinson's-Related Hallucinations: A Focus on Pimavanserin, Quetiapine and Clozapine.

  2024cites this paper
• Investigation of Safety Profile of Lurasidone and Olanzapine in Treatment of Schizophrenia

  2024cites this paper
• Neuroprotective and Neurite Outgrowth Stimulating Effects of New Low-Basicity 5-HT7 Receptor Agonists: In Vitro Study in Human Neuroblastoma SH-SY5Y Cells

  2024cites this paper
• Cell surface receptor-mediated signaling in CNS regeneration.

  2024cites this paper
• Targeting serotonin receptors with phytochemicals – an in-silico study

  2024cites this paper
• Executive dysfunction is associated with altered hippocampal-prefrontal functional connectivity in 3xTg Alzheimer’s model mice

  2024cites this paper
• Finding Drug Repurposing Candidates for Neurodegenerative Diseases using Zebrafish Behavioral Profiles

  2023cites this paper
• Advances in Alzheimer’s disease’s pharmacological treatment

  2023influential citation
• Dual Molecules Targeting 5-HT6 and GABA-A Receptors as a New Approach to Combat Depression Associated with Neuroinflammation

  2023cites this paper
• Current Fragment-to-Lead Approaches Starting From the 7-Azaindole: The Pharmacological Versatility of a Privileged Molecular Fragment.

  2023cites this paper
• Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders

  2023cites this paper
• Synthesis, computational and experimental pharmacological studies for (thio)ether-triazine 5-HT6R ligands with noticeable action on AChE/BChE and chalcogen-dependent intrinsic activity in search for new class of drugs against Alzheimer's disease.

  2023cites this paper
• Hydrophobicity modulation via the substituents at positions 2 and 4 of 1,3,5-triazine to enhance therapeutic ability against Alzheimer's disease for potent serotonin 5-HT6R agents.

  2023cites this paper
• Amisulpride decreases tau protein hyperphosphorylation in the brain of OXYS rats.

  2023cites this paper
• New Triazine Derivatives as Serotonin 5-HT6 Receptor Ligands

  2023cites this paper
• Serotonin Receptors as a Potential Target in the Treatment of Alzheimer’s Disease

  2023influential citation
• Serotonin receptors - a potential target for the treatment of Alzheimer’s disease

  2023cites this paper
• Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders

  2023cites this paper
• Impact of 5-HT6 Receptor Subcellular Localization on Its Signaling and Its Pathophysiological Roles

  2023cites this paper
• Perceiving the Concealed and Unreported Pharmacophoric Features of the 5-Hydroxytryptamine Receptor Using Balanced QSAR Analysis

  2022cites this paper
• In Silico and In Vitro Assessment of Antimicrobial and Antibiofilm Activity of Some 1,3-Oxazole-Based Compounds and Their Isosteric Analogues

  2022cites this paper
• Molecular Mechanisms of Emerging Therapeutic Targets in Alzheimer’s Disease: A Systematic Review

  2022cites this paper
• Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.

  2022cites this paper
• Synthesis, Characterization, and Biological Evaluation of Novel N-{4-[(4-Bromophenyl)sulfonyl]benzoyl}-L-valine Derivatives

  2022cites this paper
• Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

  2022cites this paper
• In Silico Screening of Natural Compounds for Candidates 5HT6 Receptor Antagonists against Alzheimer’s Disease

  2022cites this paper
• The Phenoxyalkyltriazine Antagonists for 5-HT6 Receptor with Promising Procognitive and Pharmacokinetic Properties In Vivo in Search for a Novel Therapeutic Approach to Dementia Diseases

  2021cites this paper