Abstract
Alzheimers disease (AD) is associated to a gradual loss of attention and memory that have been associated to impairment of brain cholinergic neurotransmission, particularly a deficit of cholinergic neurons in the nucleus basalis of Meynert. Thus, it is not surprising that the first therapeutic target that has demonstrated therapeutic efficacy on cognition, behaviour and functional daily activities has been the inhibitors of acetylcholinesterase (AChE), i.e. tacrine, donepezil, rivastigmine and galanthamine. But not all inhibitors of AChE have the same potency to block the enzyme and have a different pharmacological profile. For instance, rivastigmine is a dual inhibitor of AChE and butyrylcholinesterase (BuChE), and galanthamine is a mild inhibitor of AChE and an allosteric potentiating ligand of neuronal nicotinic receptors for acetylcholine (nAChRs). In addition, we have recently found that galanthamine has neuroprotective effects by inducing calcium signals and the induction of the antiapoptotic protein Bcl-2. In this frame, we have been synthesizing new tacrine derivatives that keep their ability to inhibit AChE but that interfere with neuronal calcium overloading and prevent apoptosis. Some of these compounds exhibit neuroprotecting properties and thus, could be useful in the treatment of neurodegenerative and ischaemic brain diseases.
Keywords: ad, neurodegenerative diseases, amyloid, ach, nachr, ache/buche inhibitors, tacrine, galanthamine, rivastigmine
Current Pharmaceutical Design
Title: New Classes of AChE Inhibitors with Additional Pharmacological Effects of Interest for the Treatment of Alzheimers Disease
Volume: 10 Issue: 25
Author(s): M. Villarroya, A. G. García and J. L. Marco
Affiliation:
Keywords: ad, neurodegenerative diseases, amyloid, ach, nachr, ache/buche inhibitors, tacrine, galanthamine, rivastigmine
Abstract: Alzheimers disease (AD) is associated to a gradual loss of attention and memory that have been associated to impairment of brain cholinergic neurotransmission, particularly a deficit of cholinergic neurons in the nucleus basalis of Meynert. Thus, it is not surprising that the first therapeutic target that has demonstrated therapeutic efficacy on cognition, behaviour and functional daily activities has been the inhibitors of acetylcholinesterase (AChE), i.e. tacrine, donepezil, rivastigmine and galanthamine. But not all inhibitors of AChE have the same potency to block the enzyme and have a different pharmacological profile. For instance, rivastigmine is a dual inhibitor of AChE and butyrylcholinesterase (BuChE), and galanthamine is a mild inhibitor of AChE and an allosteric potentiating ligand of neuronal nicotinic receptors for acetylcholine (nAChRs). In addition, we have recently found that galanthamine has neuroprotective effects by inducing calcium signals and the induction of the antiapoptotic protein Bcl-2. In this frame, we have been synthesizing new tacrine derivatives that keep their ability to inhibit AChE but that interfere with neuronal calcium overloading and prevent apoptosis. Some of these compounds exhibit neuroprotecting properties and thus, could be useful in the treatment of neurodegenerative and ischaemic brain diseases.
Export Options
About this article
Cite this article as:
Villarroya M., García G. A. and Marco L. J., New Classes of AChE Inhibitors with Additional Pharmacological Effects of Interest for the Treatment of Alzheimers Disease, Current Pharmaceutical Design 2004; 10 (25) . https://dx.doi.org/10.2174/1381612043383368
DOI https://dx.doi.org/10.2174/1381612043383368 |
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
-
Multi-Nutrient Dietary Intervention Approach to the Management of Alzheimer’s Disease – A Mini-Review
Current Alzheimer Research Challenges and Successes Using Nanomedicines for Aerosol Delivery to the Airways
Current Gene Therapy Clinical Applications of Positron Emission Tomography (PET) Imaging in Medicine: Oncology, Brain Diseases and Cardiology
Current Radiopharmaceuticals Mining Sarcomas by Proteomics Approaches: Ewing Sarcoma on the Spotlight
Recent Patents on Biotechnology The Role of microRNA in Ischemic and Hemorrhagic Stroke
Current Drug Delivery The Delicate Equilibrium between Oxidants and Antioxidants in Brain Glioma
Current Neuropharmacology From the Chemistry of Epoxy-Sugar Nucleosides to the Discovery of Anti-HIV Agent 4'-ethynylstavudine-Festinavir
Current Pharmaceutical Design Indoleamine 2,3-dioxygenase (IDO): Biology and Target in Cancer Immunotherapies
Current Cancer Drug Targets The Prostaglandin Agonist Beraprost Aggravates Doxorubicin-mediated Apoptosis by Increasing iNOS Expression in Cardiomyocytes
Current Vascular Pharmacology Exfoliated Epithelial Cells: A Non-Invasive way to Evaluate the Physiological State of Gastrointestinal Epithelium
Recent Patents on Biomedical Engineering (Discontinued) Polysaccharides to Combat Viruses (COVID-19) and Microbes: New updates
Current Molecular Pharmacology Nutrigenomics, β-Cell Function and Type 2 Diabetes
Current Genomics α7 Nicotinic Acetylcholine Receptors: A Therapeutic Target in the Structure Era
Current Drug Targets An Evidence-Based Systematic Review of Stevia by the Natural Standard Research Collaboration
Cardiovascular & Hematological Agents in Medicinal Chemistry Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents
Current Medicinal Chemistry Resveratrol as a Protective Molecule for Neuroinflammation: A Review of Mechanisms
Current Pharmaceutical Biotechnology Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential
Current Pharmaceutical Design p38 MAP Kinase Inhibitors as Potential Therapeutic Drugs for Neural Diseases
Central Nervous System Agents in Medicinal Chemistry Synthesis and Evaluation of Haloacetyl, α-Bromoacryloyl and Nitrooxyacetyl Benzo[b]furan and Benzo[b]thiophene Derivatives as Potent Antiproliferative Agents Against Leukemia L1210 and K562 Cells
Letters in Drug Design & Discovery Molecular Targets of Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued)