Abstract
Existing cholinesterase (ChE) inhibitor therapies for Alzheimers disease (AD), while effective in improving cognitive, behavioral and functional impairments, do not alter disease progression. Novel drug design studies have focused on the classical ChE inhibitor, (-)-physostigmine, producing alterations in chemical composition and threedimensional structure, which may offer an improved therapeutic index. The phenylcarbamate derivative, (-)-phenserine, is a selective, non-competitive inhibitor of acetylcholinesterase (AChE). In vivo, (-)-phenserine produces rapid, potent, and long-lasting AChE inhibition. As a possible result of its preferential brain selectivity, (-)-phenserine is significantly less toxic than (-)-physostigmine. In studies using the Stone maze paradigm, (-)-phenserine has been shown to improve cognitive performance in both young learning-impaired and elderly rats. In addition to reducing inactivation of acetylcholine in the brain, (-)-phenserine appears to have a second mode of action. Reduced secretion of beta-amyloid (Aβ) has been observed in cell lines exposed to (-)-phenserine, occurring through translational regulation of beta-amyloid precursor protein (β-APP) mRNA via a non-cholinergic mechanism. These in vitro findings appear to translate in vivo into animal models and humans. In a small study of patients with AD, (-)-phenserine treatment tended to reduce β-APP and Aβ levels in plasma samples. Clinical studies also reveal that (-)-phenserine (5-10 mg b.i.d.) had a favorable safety and pharmacological profile, produced significant improvements in cognitive function and was well tolerated in patients with AD treated for 12 weeks. Further randomized, double-blind, placebo-controlled Phase III studies assessing the efficacy, safety/tolerability and potential disease-modifying effects of (-)-phenserine in patients with AD are currently ongoing.
Keywords: alzheimers disease, phenserine, cholinesterase inhibitor, beta-amyloid, cognitive function, disease modification
Current Alzheimer Research
Title: An Overview of Phenserine Tartrate, A Novel Acetylcholinesterase Inhibitor for the Treatment of Alzheimers Disease
Volume: 2 Issue: 3
Author(s): Nigel H. Greig, Kumar Sambamurti, Qian-sheng Yu, Arnold Brossi, Gosse B. Bruinsma and Debomoy K. Lahiri
Affiliation:
Keywords: alzheimers disease, phenserine, cholinesterase inhibitor, beta-amyloid, cognitive function, disease modification
Abstract: Existing cholinesterase (ChE) inhibitor therapies for Alzheimers disease (AD), while effective in improving cognitive, behavioral and functional impairments, do not alter disease progression. Novel drug design studies have focused on the classical ChE inhibitor, (-)-physostigmine, producing alterations in chemical composition and threedimensional structure, which may offer an improved therapeutic index. The phenylcarbamate derivative, (-)-phenserine, is a selective, non-competitive inhibitor of acetylcholinesterase (AChE). In vivo, (-)-phenserine produces rapid, potent, and long-lasting AChE inhibition. As a possible result of its preferential brain selectivity, (-)-phenserine is significantly less toxic than (-)-physostigmine. In studies using the Stone maze paradigm, (-)-phenserine has been shown to improve cognitive performance in both young learning-impaired and elderly rats. In addition to reducing inactivation of acetylcholine in the brain, (-)-phenserine appears to have a second mode of action. Reduced secretion of beta-amyloid (Aβ) has been observed in cell lines exposed to (-)-phenserine, occurring through translational regulation of beta-amyloid precursor protein (β-APP) mRNA via a non-cholinergic mechanism. These in vitro findings appear to translate in vivo into animal models and humans. In a small study of patients with AD, (-)-phenserine treatment tended to reduce β-APP and Aβ levels in plasma samples. Clinical studies also reveal that (-)-phenserine (5-10 mg b.i.d.) had a favorable safety and pharmacological profile, produced significant improvements in cognitive function and was well tolerated in patients with AD treated for 12 weeks. Further randomized, double-blind, placebo-controlled Phase III studies assessing the efficacy, safety/tolerability and potential disease-modifying effects of (-)-phenserine in patients with AD are currently ongoing.
Export Options
About this article
Cite this article as:
Greig H. Nigel, Sambamurti Kumar, Yu Qian-sheng, Brossi Arnold, Bruinsma B. Gosse and Lahiri K. Debomoy, An Overview of Phenserine Tartrate, A Novel Acetylcholinesterase Inhibitor for the Treatment of Alzheimers Disease, Current Alzheimer Research 2005; 2 (3) . https://dx.doi.org/10.2174/1567205054367829
DOI https://dx.doi.org/10.2174/1567205054367829 |
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
-
Cannabinoid System as a Potential Target for Drug Development in the Treatment of Cardiovascular Disease
Current Vascular Pharmacology Secondary Neoplasms in Children Treated for Cancer
Current Pediatric Reviews Melatonin Receptor as a Drug Target for Neuroprotection
Current Molecular Pharmacology Intracompartmental Delivery of CNTF as Therapy for Huntingtons Disease and Retinitis Pigmentosa
Current Gene Therapy Molecular Cytogenetics of Autism
Current Genomics Small Peptide and Protein-based Molecular Probes for Imaging Neurological Diseases
Current Protein & Peptide Science Prospects for Rational Development of Pharmacological Gap Junction Channel Blockers
Current Drug Targets Functional Role of Glycosphingolipids in Cancer
Current Medicinal Chemistry Targeting Drug-Resistant Prostate Cancer with Dual PI3K/mTOR Inhibition
Current Medicinal Chemistry The Gene Expression Profiles of Medulloblastoma Cell Lines Resistant to Preactivated Cyclophosphamide
Current Cancer Drug Targets Topotecan and Irinotecan in the Treatment of Pediatric Solid Tumors
Current Pediatric Reviews In Situ Modulation of Oxidative Stress: A Novel and Efficient Strategy to Kill Cancer Cells
Current Medicinal Chemistry Epigenetic Regulation of ABCB1 Transporter Expression and Function
Current Pharmacogenomics and Personalized Medicine Dietary Fat and Hypertension: A Novel Approach Through the Proteolytic Regulatory Enzymes of the Renin-Angiotensin-System
Cardiovascular & Hematological Agents in Medicinal Chemistry Multidrug-Resistance (MDR) Proteins Develops Refractory Epilepsy Phenotype:Clinical and Experimental Evidences
Current Drug Therapy Medicinal Research Progress of Natural Coumarin and its Derivatives
The Natural Products Journal Vascular Endothelial Growth Factor as an Anti-Angiogenic Target for Cancer Therapy
Current Drug Targets Spectroscopic Characterization of a Pyridine Alkaloid from an Endophytic Strain of the Fusarium incarnatum-equiseti Species Complex
Current Bioactive Compounds Targeted Delivery of Anti-Inflammatory Agents to Tumors
Current Pharmaceutical Design Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry