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the first approved drug for the AD disease treatment, has been reported to be a multitargeted drug, however it was withdrawn from the market particularly due to its hepatotoxicity.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 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
The prediction of response to Galantamine treatment in Patients with mild to moderate Alzheimer’s Disease
Current Alzheimer Research RNAi for the Treatment of Prion Disease: A Window for Intervention in Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Antiplatelet Treatment in Peripheral Arterial Disease: The Role of Novel Antiplatelet Agents
Current Pharmaceutical Design Androgen Therapy in Male Patients Suffering from Type 2 Diabetes: A Review of Benefits and Risks
Current Diabetes Reviews Inflammatory Process as a Determinant Factor for the Degeneration of Substantia Nigra Dopaminergic Neurons: Possible Relevance to the Etiology of Parkinsons Disease
Current Medicinal Chemistry - Central Nervous System Agents Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer's Disease
Current Alzheimer Research Non-Analgesic Effects of Opioids: Opioid-induced Nausea and Vomiting: Mechanisms and Strategies for their Limitation
Current Pharmaceutical Design Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Current Neuropharmacology Update on the Pharmacological Treatment of Alzheimers Disease
Current Neuropharmacology Glial Cells – The Key Elements of Alzheimer´s Disease
Current Alzheimer Research Prognostic Significance of Homocysteine Levels in Acute Ischemic Stroke: A Prospective Cohort Study
Current Neurovascular Research Modulation of Neuro-Inflammation and Vascular Response by Oxidative Stress Following Cerebral Ischemia-Reperfusion Injury
Current Medicinal Chemistry Natural Steroids and Androgen Antagonists used as Neuroprotection in Common Neurological Disorders
CNS & Neurological Disorders - Drug Targets Alzheimers Disease and P300: Review and Evaluation of Task and Modality
Current Alzheimer Research Big Science for Small Cells: Systems Approaches for Platelets
Current Drug Targets Maternal Fish Oil Supplementation: The Prodrom of Synaptic Protection in Alzheimers Disease
Current Nutrition & Food Science 4-Acetamidobenzaldehyde Derivatives as Biological Active Candidates; Synthesis, Anti-oxidant, Anti-Alzheimer and DNA Binding Studies
Letters in Drug Design & Discovery Neuroprotective Effects of Estrogens: Cross-Talk Between Estrogen and Intracellular Insulin Signalling
Infectious Disorders - Drug Targets Vaccination of Older Adults with Dementia Against Respiratory Infections
Infectious Disorders - Drug Targets Cell to Cell Spreading of Misfolded Proteins as a Therapeutic Target in Motor Neuron Disease
Current Medicinal Chemistry