Abstract
Agonists and positive allosteric modulators of the α7 nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimers disease. This review describes the neurobiological properties of the α7 nAChR and the cognitive effects of α7 nAChR activation, focusing on the translational aspects in the development of these drugs. The functional properties and anatomical localization of the α7 nAChR makes it well suited to modulate cognitive function. Accordingly, systemic administration of α7 nAChR agonists improves learning, memory, and attentional function in variety of animal models, and procognitive effects of α7 nAChR agonists have recently been demonstrated in patients with schizophrenia or Alzheimers disease. The α7 nAChR desensitizes rapidly in vitro, and this has been a major concern in the development of α7 nAChR agonists as putative drugs. Our review of the existing literature shows that development of tolerance to the behavioral effects of α7 nAChR agonists does not occur in animal models or humans. However, the long-term memory-enhancing effects seen in animal models are not mimicked in healthy humans and schizophrenic patients, where attentional improvement predominates. This discrepancy may result from inherent differences in testing methods or from species differences in the level of expression of α7 nAChRs in limbic brain regions, and may hamper preclinical evaluation of α7 nAChR activation. It is therefore important to consider the translational power of the animal models used before entering into a clinical evaluation of the pro-cognitive effects of α7 nAChR activation.
Keywords: Nicotine, Alzheimer's disease, schizophrenia, attention, working memory, prefrontal cortex, hippocampus, acetylcholine
Current Pharmaceutical Design
Title: Cognitive Improvement by Activation of α7 Nicotinic Acetylcholine Receptors: From Animal Models to Human Pathophysiology
Volume: 16 Issue: 3
Author(s): Morten S. Thomsen, Henrik H. Hansen, Mikkelsen B. Timmerman and Jens D. Mikkelsen
Affiliation:
Keywords: Nicotine, Alzheimer's disease, schizophrenia, attention, working memory, prefrontal cortex, hippocampus, acetylcholine
Abstract: Agonists and positive allosteric modulators of the α7 nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimers disease. This review describes the neurobiological properties of the α7 nAChR and the cognitive effects of α7 nAChR activation, focusing on the translational aspects in the development of these drugs. The functional properties and anatomical localization of the α7 nAChR makes it well suited to modulate cognitive function. Accordingly, systemic administration of α7 nAChR agonists improves learning, memory, and attentional function in variety of animal models, and procognitive effects of α7 nAChR agonists have recently been demonstrated in patients with schizophrenia or Alzheimers disease. The α7 nAChR desensitizes rapidly in vitro, and this has been a major concern in the development of α7 nAChR agonists as putative drugs. Our review of the existing literature shows that development of tolerance to the behavioral effects of α7 nAChR agonists does not occur in animal models or humans. However, the long-term memory-enhancing effects seen in animal models are not mimicked in healthy humans and schizophrenic patients, where attentional improvement predominates. This discrepancy may result from inherent differences in testing methods or from species differences in the level of expression of α7 nAChRs in limbic brain regions, and may hamper preclinical evaluation of α7 nAChR activation. It is therefore important to consider the translational power of the animal models used before entering into a clinical evaluation of the pro-cognitive effects of α7 nAChR activation.
Export Options
About this article
Cite this article as:
Thomsen S. Morten, Hansen H. Henrik, Timmerman B. Mikkelsen and Mikkelsen D. Jens, Cognitive Improvement by Activation of α7 Nicotinic Acetylcholine Receptors: From Animal Models to Human Pathophysiology, Current Pharmaceutical Design 2010; 16 (3) . https://dx.doi.org/10.2174/138161210790170094
DOI https://dx.doi.org/10.2174/138161210790170094 |
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
-
Glycobiology of Neural Stem Cells
CNS & Neurological Disorders - Drug Targets Longitudinal Functional MRI of Motor and Cognitive Recovery Following Stroke: A Review
Current Medical Imaging HIV-1 Induced CNS Dysfunction: Current Overview and Research Priorities
Current HIV Research Histone Deacetylase Inhibitors: Therapeutic Agents and Research Tools for Deciphering Motor Neuron Diseases
Current Medicinal Chemistry Sodium Valproate Induced Tremor in a Patient with Epilepsy and Down's Syndrome
Current Drug Safety Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy
Current Neurovascular Research Dynamic Expression of MicroRNAs (183, 135a, 125b, 128, 30c and 27a) in the Rat Pilocarpine Model and Temporal Lobe Epilepsy Patients
CNS & Neurological Disorders - Drug Targets The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity
Current Neuropharmacology Commonalities in Biological Pathways, Genetics, and Cellular Mechanism between Alzheimer Disease and Other Neurodegenerative Diseases: An In Silico-Updated Overview
Current Alzheimer Research Gene Therapy for Angelman Syndrome: Contemporary Approaches and Future Endeavors
Current Gene Therapy Concentration-Dependent Bimodal Effect of Specific 18 kDa Translocator Protein (TSPO) Ligands on Cell Death Processes Induced by Ammonium Chloride: Potential Implications for Neuropathological Effects Due to Hyperammonemia
CNS & Neurological Disorders - Drug Targets Serotonin<sub>2c</sub> Receptor Constitutive Activity: In vivo Direct and Indirect Evidence and Functional Significance
Central Nervous System Agents in Medicinal Chemistry Neuroimaging of the Serotonin Transporter: Possibilities and Pitfalls
Current Psychiatry Reviews Design and Synthesis of New Selective P-gp Substrates and Inhibitors
Current Pharmaceutical Design The Role of Physical Exercise and Omega-3 Fatty Acids in Depressive Illness in the Elderly
Current Neuropharmacology Pharmacological Management of Huntingtons Disease: An Evidence- Based Review
Current Pharmaceutical Design Variability of Biological Activities of Limonoids Derived from Plant Sources
Mini-Reviews in Organic Chemistry The Hypothalamus and Obesity
Recent Patents on CNS Drug Discovery (Discontinued) Drug-Resistance in Central Nervous System Tumors: From the Traditional Cell-Resistance Model to the Genetically Driven Approaches on Therapy
Current Pharmaceutical Biotechnology GABAergic Pharmacotherapy in the Treatment of Motor Disorders of the Central Nervous System
Current Pharmaceutical Design