Abstract
Background: Cognitive deficits are amongst the most socially debilitating and least effectively treated symptoms of schizophrenia. The cholinergic system is a promising target for the design of novel drugs that can more effectively treat these symptoms. Methods: We review the literature supporting the dysfunction of the cholinergic system in schizophrenia, discuss the preclinical and clinical data showing that modulating the cholinergic system could improve the symptoms of schizophrenia and review the main pharmacological strategies being investigated to treat cholinergic dysfunction in schizophrenia. Results: Post-mortem and neuroimaging studies suggest there are widespread reductions in cholinergic receptor signalling in the cortex as well as subcortical regions, such as the hippocampus and striatum, in individuals with schizophrenia. Potential cholinergic drug targets are being pursued to increase receptor function. These include inhibiting the activity of the enzyme acetylcholinesterase to increase synaptic acetylcholine levels, and increasing the nicotinic receptor and muscarinic receptor activity with agonists or positive allosteric modulators. Conclusion: Amongst the most promising drug targets for treating schizophrenia are the α7 nicotinic receptor and the CHRM1 and CHRM4 muscarinic receptors. The recent development of allosteric modulators that selectively target these receptors offers the potential to more effectively treat the symptoms of schizophrenia.
Keywords: Schizophrenia, acetylcholine, cholinesterase inhibitors, muscarinic receptors, nicotinic receptors, positive allosteric modulators.
Current Pharmaceutical Design
Title:The Cholinergic System: An Emerging Drug Target for Schizophrenia
Volume: 22 Issue: 14
Author(s): Andrew Gibbons and Brian Dean
Affiliation:
Keywords: Schizophrenia, acetylcholine, cholinesterase inhibitors, muscarinic receptors, nicotinic receptors, positive allosteric modulators.
Abstract: Background: Cognitive deficits are amongst the most socially debilitating and least effectively treated symptoms of schizophrenia. The cholinergic system is a promising target for the design of novel drugs that can more effectively treat these symptoms. Methods: We review the literature supporting the dysfunction of the cholinergic system in schizophrenia, discuss the preclinical and clinical data showing that modulating the cholinergic system could improve the symptoms of schizophrenia and review the main pharmacological strategies being investigated to treat cholinergic dysfunction in schizophrenia. Results: Post-mortem and neuroimaging studies suggest there are widespread reductions in cholinergic receptor signalling in the cortex as well as subcortical regions, such as the hippocampus and striatum, in individuals with schizophrenia. Potential cholinergic drug targets are being pursued to increase receptor function. These include inhibiting the activity of the enzyme acetylcholinesterase to increase synaptic acetylcholine levels, and increasing the nicotinic receptor and muscarinic receptor activity with agonists or positive allosteric modulators. Conclusion: Amongst the most promising drug targets for treating schizophrenia are the α7 nicotinic receptor and the CHRM1 and CHRM4 muscarinic receptors. The recent development of allosteric modulators that selectively target these receptors offers the potential to more effectively treat the symptoms of schizophrenia.
Export Options
About this article
Cite this article as:
Gibbons Andrew and Dean Brian, The Cholinergic System: An Emerging Drug Target for Schizophrenia, Current Pharmaceutical Design 2016; 22 (14) . https://dx.doi.org/10.2174/1381612822666160127114010
DOI https://dx.doi.org/10.2174/1381612822666160127114010 |
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
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...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
- 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
-
Natural Compounds Used as Therapies Targeting to Amyotrophic Lateral Sclerosis
Current Pharmaceutical Biotechnology Gene Therapy as a Novel Pharmaceutical Intervention for Stroke
Current Pharmaceutical Design Tumor Necrosis Factor Blocking Therapy and Congestive Heart Failure in Patients with Inflammatory Rheumatic Disorders: A Systematic Review
Current Medicinal Chemistry Proteasome Inhibition: A Promising Strategy for Treating Cancer, but What About Neurotoxicity?
Current Medicinal Chemistry Multipotent, Permeable Drug ASS234 Inhibits Aβ Aggregation, Possesses Antioxidant Properties and Protects from Aβ-induced Apoptosis In Vitro
Current Alzheimer Research Therapeutic Efficacy of Selegiline in Neurodegenerative Disorders and Neurological Diseases
Current Drug Targets Diabetes NEP-Like Endopeptidases and Alzheimers Disease
Current Alzheimer Research Cerebral Microemboli Increase β-amyloid Protein Deposition, MMP-9, and GFAP Expression in the Alzheimer`s Model of APP/PS1 Double Transgenic Mice
Current Neurovascular Research Editorial [Hot topic: Adenosine Receptor Ligands: Where Are We, and Where Are We Going? (Guest Editors: Tiziano Tuccinardi and Adriano Martinelli)]
Current Topics in Medicinal Chemistry Simvastatin and Other HMG-CoA Reductase Inhibitors on Brain Cholesterol Levels in Alzheimers Disease
Current Alzheimer Research Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Central Nervous System Agents in Medicinal Chemistry Novel Anticoagulants vs Warfarin for Stroke Prevention in Atrial Fibrillation
Cardiovascular & Hematological Disorders-Drug Targets Why and How We Should Treat Elderly Patients with Hypertension?
Current Vascular Pharmacology New Molecular Avenues in Parkinson ’ s Disease Therapy
Current Topics in Medicinal Chemistry Differential Cued-Stroop Performance in Cognitively Asymptomatic Older Adults with Biomarker-Identified Risk for Alzheimer’s Disease: A Pilot Study
Current Alzheimer Research Capsaicin and Its Analogues: Structure-Activity Relationship Study
Current Medicinal Chemistry Disturbed Sleep Patterns in Elders with Mild Cognitive Impairment: The Role of Memory Decline and ApoE ε 4 Genotype
Current Alzheimer Research Cytotoxicity and Toxicity to Animals and Humans of Ribosome-Inactivating Proteins
Mini-Reviews in Medicinal Chemistry Electromagnetic Field: A Potential Innovative Treatment for Alzheimer’s Disease
Current Psychiatry Research and Reviews M1 Muscarinic Agonists Target Major Hallmarks of Alzheimers Disease – an Update
Current Alzheimer Research