Abstract
Alzheimer´s disease (AD) is a progressive neurodegenerative dementia which currently represents one of the biggest threats for the human kind. The cure is still unknown and various hypotheses (cholinergic, amyloidal, oxidative, vascular etc.) are investigated in order to understand the pathophysiology of the disease and on this basis find an effective treatment. Tacrine, the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug, however it was withdrawn from the market particularly due to its hepatotoxicity. Its derivative 7-methoxytacrine (7- MEOTA) probably due to the different metabolization does not exert this side effect. The aim of our study was to compare these two cholinesterase inhibitors from various, mainly cholinergic, points of view relevant for a potential AD drug. We found that 7-MEOTA does not fall behind its more well-known parent compound – tacrine. Furthermore, we found, that 7-MEOTA exerts better properties in most of the tests related to a possible AD treatment. Only the pharmacokinetics and a higher acetylcholinesterase and butyrylcholinesterase inhibitory potency would slightly give advantages to tacrine over 7-MEOTA, but concerning its lower toxicity, better antioxidant properties, interaction with muscarinic and nicotinic receptors and “safer” metabolization provide strong evidence for reconsider 7-MEOTA and its derivatives as candidate molecules for the treatment of AD.
Keywords: 7-Methoxytacrine, Acetylcholinesterase inhibitor, Alzheimer´s disease drug, Cholinergic hypothesis, Pharmacological profile, Tacrine.
Current Alzheimer Research
Title:A Resurrection of 7-MEOTA: A Comparison with Tacrine
Volume: 10 Issue: 8
Author(s): Ondrej Soukup, Daniel Jun, Jana Zdarova-Karasova, Jiri Patocka, Kamil Musilek, Jan Korabecny, Jan Krusek, Martina Kaniakova, Vendula Sepsova, Jana Mandikova, Frantisek Trejtnar, Miroslav Pohanka, Lucie Drtinova, Michal Pavlik, Gunnar Tobin and Kamil Kuca
Affiliation:
Keywords: 7-Methoxytacrine, Acetylcholinesterase inhibitor, Alzheimer´s disease drug, Cholinergic hypothesis, Pharmacological profile, Tacrine.
Abstract: Alzheimer´s disease (AD) is a progressive neurodegenerative dementia which currently represents one of the biggest threats for the human kind. The cure is still unknown and various hypotheses (cholinergic, amyloidal, oxidative, vascular etc.) are investigated in order to understand the pathophysiology of the disease and on this basis find an effective treatment. Tacrine, the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug, however it was withdrawn from the market particularly due to its hepatotoxicity. Its derivative 7-methoxytacrine (7- MEOTA) probably due to the different metabolization does not exert this side effect. The aim of our study was to compare these two cholinesterase inhibitors from various, mainly cholinergic, points of view relevant for a potential AD drug. We found that 7-MEOTA does not fall behind its more well-known parent compound – tacrine. Furthermore, we found, that 7-MEOTA exerts better properties in most of the tests related to a possible AD treatment. Only the pharmacokinetics and a higher acetylcholinesterase and butyrylcholinesterase inhibitory potency would slightly give advantages to tacrine over 7-MEOTA, but concerning its lower toxicity, better antioxidant properties, interaction with muscarinic and nicotinic receptors and “safer” metabolization provide strong evidence for reconsider 7-MEOTA and its derivatives as candidate molecules for the treatment of AD.
Export Options
About this article
Cite this article as:
Soukup Ondrej, Jun Daniel, Zdarova-Karasova Jana, Patocka Jiri, Musilek Kamil, Korabecny Jan, Krusek Jan, Kaniakova Martina, Sepsova Vendula, Mandikova Jana, Trejtnar Frantisek, Pohanka Miroslav, Drtinova Lucie, Pavlik Michal, Tobin Gunnar and Kuca Kamil, A Resurrection of 7-MEOTA: A Comparison with Tacrine, Current Alzheimer Research 2013; 10 (8) . https://dx.doi.org/10.2174/1567205011310080011
DOI https://dx.doi.org/10.2174/1567205011310080011 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Amino Thiols, Detoxification and Oxidative Stress in Pre-Eclampsia and Other Disorders of Pregnancy
Current Pharmaceutical Design Validity of Oxygen-Ozone Therapy as Integrated Medication Form in Chronic Inflammatory Diseases
Cardiovascular & Hematological Disorders-Drug Targets Positive Social Interactions in a Lifespan Perspective with a Focus on Opioidergic and Oxytocinergic Systems: Implications for Neuroprotection
Current Neuropharmacology MMP Inhibitors in Cardiac Diseases: An Update
Recent Patents on Cardiovascular Drug Discovery Predictors of Conversion to Dementia of Probable Alzheimer Type in Patients with Mild Cognitive Impairment
Current Alzheimer Research Fighting Alzheimer's Disease and Type 2 Diabetes: Pathological links and Treatment Strategies
CNS & Neurological Disorders - Drug Targets Protein Kinase CK2 in Human Diseases
Current Medicinal Chemistry Annexin A5 Imaging: An Academic Research – Clinical Trials and Theses
Current Molecular Imaging (Discontinued) New Targets for Treating the Underlying Pathophysiology and Nonmotor Aspects of Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Sirtuins: Common Targets in Aging and in Neurodegeneration
Current Drug Targets Applications of Arterial Spin Labelling in Mild Cognitive Impairment, Alzheimers Disease and Other Forms of Dementia
Current Medical Imaging Neurobiological Mechanisms of Stress Resilience and Implications for the Aged Population
Current Neuropharmacology Endocannabinoids and their Involvement in the Neurovascular System
Current Neurovascular Research Current Understanding of Central Nervous System Drainage Systems: Implications in the Context of Neurodegenerative Diseases
Current Neuropharmacology Programmed Cell Death Mechanisms in Neurological Disease
Current Molecular Medicine Transthyretin Decrease in Plasma of MCI and AD Patients: Investigation of Mechanisms for Disease Modulation
Current Alzheimer Research Phenylbutyric Acid Protects Against Spatial Memory Deficits in a Model of Repeated Electroconvulsive Therapy
Current Neurovascular Research Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia
Current Neurovascular Research Efficient and Green Synthetic Protocol for the Synthesis of Structurally Diverse Spiroheterocycles using GAAS as Catalytic Solvent
Current Organocatalysis Patent Selections:
Recent Patents on CNS Drug Discovery (Discontinued)