Abstract
Despite advances in understanding the pathophysiology of Alzheimer’s disease (AD), its therapy remains largely symptomatic and supportive. Acetylcholinesterase inhibitors - the first-line drugs used today do not prevent and treat AD. So far, over 90 Phase 3 trials of AD have been unsuccessful with 99.0% failure rate. There is, therefore, an urgent need to find effective new therapies for AD. Owing to the multifactorial nature of AD pathogenesis, polypharmacy with drugs that target heterogeneous pathophysiological pathways, needs to be considered. Fortunately, several drugs used currently in clinical use as monotherapies can be exploited in AD. This article, therefore, presents a novel pharmacological treatment paradigm and recommends the use of valuable diseasemodifying approved drugs, viz. melatonin, minocycline, modafinil, and memantine (the “M” Drugs). Melatonin - a neuroprotector is an antioxidant and anti-inflammatory. Minocycline is also neuroprotective, it reduces neuroinflammation and CNS pathology and prevents cell death. Sleep deprivation leads to decreased hippocampal neurogenesis, increased amyloid beta generation, and causes memory dysfunction. Modafinil - a wake-promoting agent is approved for use in narcolepsy and obstructive sleep apnea. It improves global mental status, hippocampal neurogenesis, attention, and cognition. Memantine is an uncompetitive N-methyl-d-aspartic acid receptor antagonist and is approved for the management of moderate-to-severe AD. The paramount possible beneficial effects of the M-drugs may include significant memory and cognitive enhancement in aging, mild cognitive impairment, and AD. The M drugs-centric pharmacotherapy strategy is comprehensive and pragmatic and is meant to combat multiple pathological targets and ameliorate cognitive dysfunction/AD.
Keywords: Alzheimer’s disease, inflammation, oxidative and nitrosative stress, Melatonin, Minocycline, Modafinil, Memantine, amyloid beta, tau hyperphosphorylation.
Current Pharmaceutical Design
Title:Pharmacotherpy and Alzheimer’s Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach
Volume: 22 Issue: 16
Author(s): Mak Adam Daulatzai
Affiliation:
Keywords: Alzheimer’s disease, inflammation, oxidative and nitrosative stress, Melatonin, Minocycline, Modafinil, Memantine, amyloid beta, tau hyperphosphorylation.
Abstract: Despite advances in understanding the pathophysiology of Alzheimer’s disease (AD), its therapy remains largely symptomatic and supportive. Acetylcholinesterase inhibitors - the first-line drugs used today do not prevent and treat AD. So far, over 90 Phase 3 trials of AD have been unsuccessful with 99.0% failure rate. There is, therefore, an urgent need to find effective new therapies for AD. Owing to the multifactorial nature of AD pathogenesis, polypharmacy with drugs that target heterogeneous pathophysiological pathways, needs to be considered. Fortunately, several drugs used currently in clinical use as monotherapies can be exploited in AD. This article, therefore, presents a novel pharmacological treatment paradigm and recommends the use of valuable diseasemodifying approved drugs, viz. melatonin, minocycline, modafinil, and memantine (the “M” Drugs). Melatonin - a neuroprotector is an antioxidant and anti-inflammatory. Minocycline is also neuroprotective, it reduces neuroinflammation and CNS pathology and prevents cell death. Sleep deprivation leads to decreased hippocampal neurogenesis, increased amyloid beta generation, and causes memory dysfunction. Modafinil - a wake-promoting agent is approved for use in narcolepsy and obstructive sleep apnea. It improves global mental status, hippocampal neurogenesis, attention, and cognition. Memantine is an uncompetitive N-methyl-d-aspartic acid receptor antagonist and is approved for the management of moderate-to-severe AD. The paramount possible beneficial effects of the M-drugs may include significant memory and cognitive enhancement in aging, mild cognitive impairment, and AD. The M drugs-centric pharmacotherapy strategy is comprehensive and pragmatic and is meant to combat multiple pathological targets and ameliorate cognitive dysfunction/AD.
Export Options
About this article
Cite this article as:
Adam Daulatzai Mak, Pharmacotherpy and Alzheimer’s Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach, Current Pharmaceutical Design 2016; 22 (16) . https://dx.doi.org/10.2174/1381612822666160203142111
DOI https://dx.doi.org/10.2174/1381612822666160203142111 |
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
-
Patented Small Molecules Used for Reprogramming
Recent Patents on Regenerative Medicine Functional, Genetic and Biochemical Biomarkers of Peripheral Arterial Disease
Current Medicinal Chemistry Long-Term Treatment With Raltegravir is Associated with Lower Triglycerides and Platelets Count in the Older HIV+ Population: Results from the Ral-Age Study
Current HIV Research Treatment and Response to Statins: Gender-related Differences
Current Medicinal Chemistry Molecular Determinants of the Cardiometabolic Phenotype
Endocrine, Metabolic & Immune Disorders - Drug Targets Neuroprotective Mechanisms of Oxygen and Ethanol: A Potential Combination Therapy in Stroke
Current Medicinal Chemistry Editorial (Thematic Issue: Current Therapeutic Options in Cardiomyopathies)
Current Pharmaceutical Design Phytocannabinoids and Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Advanced Glycation End Products and Insulin Resistance
Current Pharmaceutical Design Natural and Synthetic Naphthoquinones Active Against Trypanosoma Cruzi: An Initial Step Towards New Drugs for Chagas Disease
Current Medicinal Chemistry LDL and HDL Subfractions, Dysfunctional HDL: Treatment Options
Current Pharmaceutical Design Role of Adiponectin in Obesity, Hypertension, and Metabolic Syndrome
Current Hypertension Reviews Hematocrit-lowering Effect Following Inactivation of Renin-Angiotensin System with Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
Current Topics in Medicinal Chemistry A Comprehensive Review on Phytochemistry and Pharmacological Effects of Stinging Nettle (Urtica dioica)
Current Traditional Medicine Recent Progress and Related Patents on the Applications of Bone Marrow-Derived Stem/Progenitor Cells in Regenerative Medicine and Cancer Therapies
Recent Patents on Regenerative Medicine Inflammation: A Link Between Hypertension and Atherosclerosis
Current Hypertension Reviews Metabolic Syndrome and Cardiometabolic Risk Factors
Current Vascular Pharmacology Flow and Microwave Assisted Synthesis of Medicinally Relevant Indoles
Current Green Chemistry An Insight to Colon Targeted Drug Delivery System
Drug Delivery Letters P2X7 Receptors: Channels, Pores and More
CNS & Neurological Disorders - Drug Targets