Abstract
There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and a recent trial of a drug with direct action at metabotropic glutamate autoreceptors has demonstrated equivalent efficacy to olanzapine in patients with chronic schizophrenia. Imaging the glutamate system in humans in vivo poses a number of difficulties, and has progressed slowly in comparison to the relative ease of dopamine imaging. Indirect imaging of the glutamate system is possible using pharmacological challenges targeting the glutamate system combined with fMRI, PET or SPECT imaging. There are two methods of directly estimating glutamatergic neurotransmission in living patients using neuroimaging at present: [123I]CNS-1261 SPECT (measuring NMDAR binding), and proton magnetic resonance spectroscopy (MRS) of glutamate and glutamine. Both methods have yielded some intriguing insights into glutamatergic abnormalities and their relevance to psychotic symptoms. In this review, the glutamate hypothesis of schizophrenia, and its relationship to current findings in glutamate imaging in psychosis to this hypothesis will be discussed. The possibility of developing new drugs for schizophrenia in light of these findings will then be considered.
Keywords: Schizophrenia, glutamate, glutamine, fMRI, NMDA, SPECT, PET, MRS, ketamine
Current Pharmaceutical Design
Title: Imaging the Glutamate System in Humans: Relevance to Drug Discovery for Schizophrenia
Volume: 15 Issue: 22
Author(s): James M. Stone
Affiliation:
Keywords: Schizophrenia, glutamate, glutamine, fMRI, NMDA, SPECT, PET, MRS, ketamine
Abstract: There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and a recent trial of a drug with direct action at metabotropic glutamate autoreceptors has demonstrated equivalent efficacy to olanzapine in patients with chronic schizophrenia. Imaging the glutamate system in humans in vivo poses a number of difficulties, and has progressed slowly in comparison to the relative ease of dopamine imaging. Indirect imaging of the glutamate system is possible using pharmacological challenges targeting the glutamate system combined with fMRI, PET or SPECT imaging. There are two methods of directly estimating glutamatergic neurotransmission in living patients using neuroimaging at present: [123I]CNS-1261 SPECT (measuring NMDAR binding), and proton magnetic resonance spectroscopy (MRS) of glutamate and glutamine. Both methods have yielded some intriguing insights into glutamatergic abnormalities and their relevance to psychotic symptoms. In this review, the glutamate hypothesis of schizophrenia, and its relationship to current findings in glutamate imaging in psychosis to this hypothesis will be discussed. The possibility of developing new drugs for schizophrenia in light of these findings will then be considered.
Export Options
About this article
Cite this article as:
Stone M. James, Imaging the Glutamate System in Humans: Relevance to Drug Discovery for Schizophrenia, Current Pharmaceutical Design 2009; 15 (22) . https://dx.doi.org/10.2174/138161209788957438
DOI https://dx.doi.org/10.2174/138161209788957438 |
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
-
L-Arginine in the Prevention and Treatment of Cardiovascular Disease: From Basic to Clinical Research Studies
Vascular Disease Prevention (Discontinued) How to Keep Oxidative Stress Under Control?
Current Nutrition & Food Science Perioperative Heart-Brain Axis Protection in Obese Surgical Patients: The Nutrigenomic Approach
Current Medicinal Chemistry Xanthine Oxidase Inhibitor Febuxostat as a Novel Agent Postulated to Act Against Vascular Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Restoration of Chemoresistance Mechanism by Novel Drug Therapies in Breast Cancer Cell Lines
Current Drug Therapy Potential Therapeutic Effects of Na+/Ca2+ Exchanger Inhibition in Cardiac Diseases
Current Medicinal Chemistry Pharmacological Intervention of Cyclooxygenase-2 and 5-Lipoxygenase Pathways. Impact on Inflammation and Cancer
Current Pharmaceutical Design Vitamin D and the Adaptive Immune System with Special Emphasis to Allergic Reactions and Allograft Rejection
Inflammation & Allergy - Drug Targets (Discontinued) Effect of Dipeptidyl Peptidase-4 Inhibitors on Plasma Adiponectin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Current Medicinal Chemistry N-Acetylcysteine and Other Preventive Measures for Contrast-Induced Nephropathy in the Intensive Care Unit
Current Medicinal Chemistry Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Mechanical Intervention for Acute Myocardial Infarction
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Cardiac Involvement in ANCA (+) and ANCA (-) Churg-Strauss Syndrome Evaluated by Cardiovascular Magnetic Resonance
Inflammation & Allergy - Drug Targets (Discontinued) MicroRNAs in Organogenesis and Disease
Current Molecular Medicine Sympathetic Activation in Hypertension and in Hypertension-Related Metabolic Disease
Current Hypertension Reviews Recent Patents on Proteasome Inhibitors of Natural Origin
Recent Patents on Anti-Cancer Drug Discovery Editorial (Hot Topic: Cardiovascular Disease Biomarkers: from Tradition to Modernity)
Current Topics in Medicinal Chemistry The Role of Systemic Treatment and Radiotherapy in Malignant Mesothelioma
Current Respiratory Medicine Reviews Imaging of Abdominal Aortic Aneurysm: The Present and the Future
Current Vascular Pharmacology Treatment of Hypertensive Complications in Pregnancy
Current Pharmaceutical Design Relaxin in Vascular Physiology and Pathophysiology: Possible Implications in Ischemic Brain Disease
Current Neurovascular Research