Abstract
Tacrine belongs to the group of acetylcholinesterse (AChE) inhibitors used as drugs for treatment of Alzheimers disease (AD). The formation of hydroxyderivatives of tacrine is well-established step in the metabolization of this drug in liver by microsomal cytochrome P450 enzymes family. Genetic polymorphism of cytochrome P450 enzymes is probably responsible for balance between a number of stable and non-toxic metabolites and highly protein-reactive and toxic ones. By this manner may be explained why the hepatotoxicity of tacrine was observed only in the part of persons and why not every patient with AD responds to the treatment by this drug.
Keywords: Alzheimer's disease, tacrine, metabolite, drug toxicity, P450, hydroxyderivatives
Current Drug Metabolism
Title: Possible Role of Hydroxylated Metabolites of Tacrine in Drug Toxicity and Therapy of Alzheimers Disease
Volume: 9 Issue: 4
Author(s): Jiri Patocka, Daniel Jun and Kamil Kuca
Affiliation:
Keywords: Alzheimer's disease, tacrine, metabolite, drug toxicity, P450, hydroxyderivatives
Abstract: Tacrine belongs to the group of acetylcholinesterse (AChE) inhibitors used as drugs for treatment of Alzheimers disease (AD). The formation of hydroxyderivatives of tacrine is well-established step in the metabolization of this drug in liver by microsomal cytochrome P450 enzymes family. Genetic polymorphism of cytochrome P450 enzymes is probably responsible for balance between a number of stable and non-toxic metabolites and highly protein-reactive and toxic ones. By this manner may be explained why the hepatotoxicity of tacrine was observed only in the part of persons and why not every patient with AD responds to the treatment by this drug.
Export Options
About this article
Cite this article as:
Patocka Jiri, Jun Daniel and Kuca Kamil, Possible Role of Hydroxylated Metabolites of Tacrine in Drug Toxicity and Therapy of Alzheimers Disease, Current Drug Metabolism 2008; 9 (4) . https://dx.doi.org/10.2174/138920008784220619
DOI https://dx.doi.org/10.2174/138920008784220619 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Tissue Distribution and Metabolism of Micro- and Nanoparticles and Medical Implants
With the continuous advancement of modern science and engineering, numerous functional materials and active molecules have been developed and utilized in various industrial, medical, and food applications. Many of these can enter the body, either actively or passively, and have significant and intricate impacts on human health. For example, biomaterials ...read more
Related Journals
- 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
-
In vitro Study of Furazano[3,4-b]quinoxaline 1-Oxides as Potential ΝΟ Releasing Agents
Letters in Drug Design & Discovery Signal Transduction by the Cytoplasmic Domain of NEUREGULIN-1 and its Roles During Neuronal Aging
Current Signal Transduction Therapy Subject Index To Volume 1
Recent Patents on CNS Drug Discovery (Discontinued) Role of the Transforming-Growth-Factor-β1 Gene in Late-Onset Alzheimer’s Disease: Implications for the Treatment
Current Genomics Bedside Balance Testing in Elderly People
Current Aging Science REM sleep and its Loss-Associated Epigenetic Regulation with Reference to Noradrenaline in Particular
Current Neuropharmacology Structural MRI Predictors of Late-Life Cognition Differ Across African Americans, Hispanics, and Whites
Current Alzheimer Research Is there a Possible Single Mediator in Modulating Neuroendocrine–thymus Interaction in Ageing?
Current Aging Science Factors Predisposing to Hypertension in Subjects Formerly Born Preterm: Renal Impairment, Arterial Stiffness, Endothelial Dysfunction or Something Else?
Current Hypertension Reviews Editorial: Questioning the Governance of Pharmacogenomics and Personalized Medicine for Global Health
Current Pharmacogenomics and Personalized Medicine Biological Function and Mechanism of Bone Marrow Mesenchymal Stem Cells-packed Poly (3,4-ethylenedioxythiophene) (PEDOT) Scaffolds for Peripheral Nerve Injury: The Involvement of miR-21-Notch Signaling Pathway
Current Neurovascular Research Microwave-assisted Formation of Organic Disulfides of Biochemical Significance
Current Medicinal Chemistry SELDI Protein Chip Technology for the Detection of Serum Biomarkers for Liver Disease
Protein & Peptide Letters Expression, Purification and In Silico Studies of Cold Resistant Protein from Plant Growth Promoting Ps fluorescens Mutant CRPF1
Current Biotechnology The Action of Polyphenols in Diabetes Mellitus and Alzheimer's Disease: A Common Agent for Overlapping Pathologies
Current Neuropharmacology Quantitative Enzymology
Current Enzyme Inhibition Synthetic Sphingosine 1-Phosphate Receptor Modulators - Opportunities and Potential Pitfalls
Current Topics in Medicinal Chemistry CREG: A Possible Candidate for Both Prevention and Treatment of Proliferative Vascular Disease
Current Molecular Medicine The Role of the Anti-Amyloidogenic Secretase ADAM10 in Shedding the APP-like Proteins
Current Alzheimer Research Molecular Docking Study of a Series of Substituted Xanthone Derivatives as Novel COX-2 Inhibitors Targeting Prostaglandin Endoperoxide Synthase -2
Current Enzyme Inhibition