Abstract
At present the only FDA-approved therapy for Alzheimers disease involves the administration of acetylcholinesterase inhibitors, to alleviate the cholinergic deficit associated with this disease. However, none of the approved drugs is ideal in efficacy or tolerability. One possible strategy to improve selectivity and potency is to design drugs that can simultaneously bind to the catalytic and peripheral anionic sites of AChE. In this review we will describe the development of dimeric AChE inhibitors, from the early observations of high inhibition potency by bis-quaternary inhibitors, to the structure-based design of dimers based on tacrine, huperzine A, galanthamine, and polyamines.
Keywords: acetylcholinesterase, butyrylcholinesterase, alzheimers disease, inhibitor, bivalent, dimer
Current Pharmaceutical Design
Title: Development of Bivalent Acetylcholinesterase Inhibitors as Potential Therapeutic Drugs for Alzheimers Disease
Volume: 10 Issue: 25
Author(s): Da-Ming Du and Paul R. Carlier
Affiliation:
Keywords: acetylcholinesterase, butyrylcholinesterase, alzheimers disease, inhibitor, bivalent, dimer
Abstract: At present the only FDA-approved therapy for Alzheimers disease involves the administration of acetylcholinesterase inhibitors, to alleviate the cholinergic deficit associated with this disease. However, none of the approved drugs is ideal in efficacy or tolerability. One possible strategy to improve selectivity and potency is to design drugs that can simultaneously bind to the catalytic and peripheral anionic sites of AChE. In this review we will describe the development of dimeric AChE inhibitors, from the early observations of high inhibition potency by bis-quaternary inhibitors, to the structure-based design of dimers based on tacrine, huperzine A, galanthamine, and polyamines.
Export Options
About this article
Cite this article as:
Du Da-Ming and Carlier R. Paul, Development of Bivalent Acetylcholinesterase Inhibitors as Potential Therapeutic Drugs for Alzheimers Disease, Current Pharmaceutical Design 2004; 10 (25) . https://dx.doi.org/10.2174/1381612043383412
DOI https://dx.doi.org/10.2174/1381612043383412 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
3D MI-DRAGON: New Model for the Reconstruction of US FDA Drug- Target Network and Theoretical-Experimental Studies of Inhibitors of Rasagiline Derivatives for AChE
Current Topics in Medicinal Chemistry Perioperative Considerations in Rheumatoid Arthritis Patients
Current Rheumatology Reviews Mitogenomics: Recognizing the Significance of Mitochondrial Genomic Variation for Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Lessons from Darwin: Evolutionary Biologys Implications for Alzheimers Disease Research and Patient Care
Current Alzheimer Research Cardiotoxicity of Molecularly Targeted Agents
Current Cardiology Reviews Editorial (Hot Topic: Epidemiology & Risk Factors for Alzheimer’s Disease)
Current Alzheimer Research Immunological Approaches to Prevent Neuronal Apoptosis During Neuroinflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Ceramide Involvement in Apoptosis and Apoptotic Diseases
Mini-Reviews in Medicinal Chemistry Potential Role of microRNAs in Cardiovascular Disease: Are They up to Their Hype?
Current Cardiology Reviews Oxidative Stress, Antioxidants and Neurodegenerative Diseases
Current Pharmaceutical Design NF-κB, a Potential Therapeutic Target for the Treatment of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy
Current Drug Metabolism Cerebrospinal-fluid Alzheimer’s Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson’s Disease Patients
CNS & Neurological Disorders - Drug Targets Conference Report: The American Association for the Advancement of Science (AAAS), 180th Annual Meeting Chicago, IL, USA Feb 13-17, 2014 “Meeting Global Challenges: Discoveries & Innovation”
CNS & Neurological Disorders - Drug Targets Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome
Current Alzheimer Research Antiinflammatory Activity of Melatonin in Central Nervous System
Current Neuropharmacology Nanotubes at Neural and Immune Synapses
Current Medicinal Chemistry Neurosteroid PREGS Protects Neurite Growth and Survival of Newborn Neurons in the Hippocampal Dentate Gyrus of APPswe/PS1dE9 Mice
Current Alzheimer Research Actigraphy for Assessing Light Effects on Sleep and Circadian Activity Rhythm in Alzheimer's Dementia: A Narrative Review
Current Alzheimer Research Genetic Features of MAPT, GRN, C9orf72 and CHCHD10 Gene Mutations in Chinese Patients with Frontotemporal Dementia
Current Alzheimer Research