Abstract
The development of receptor-binding radiotracers has evolved from a goal of high affinity compounds to give high target to non target ratios to compounds of slightly lesser affinity so that they can reach either steady state after bolus injection or equilibrium after infusion. The other important advance is the ability to measure endogenous neurotransmitter, using various lower affinity muscarinic acetylcholine receptor radioligands. There have been a number of clinical studies that elucidated the mechanism of action of new pharmaceuticals in vivo using external imaging. These include studies of drug interaction of olanzapine, risperidone, clozapine, donepezil, and phenserine with the muscarinic receptor. There have been fewer studies monitoring the effect of therapy in Alzheimers disease, but those pilot studies give great hope that monitoring therapy is a real possibility. Radioligands for the muscarinic receptor, for ACh esterase, and to measure the concentration of acetylcholine have now been developed, A number of studies in small populations have identified changes in mild to moderate Alzheimers disease and, perhaps more importantly, changes in radioligand binding have been identified in clinically normal subjects genetically predisposed to Alzheimers disease by virtue of the epsilon 4+ variant of the APOE gene. Large scale clinical studies are now needed to delineate the true value of these radiotracers in clinical situations. PET and SPECT imaging hold the promise of monitoring the effect of pharmaceuticals in a wide variety of diseases using non-invasive external imaging of the muscarinic cholinergic system.
Keywords: Muscarinic receptor, acetylcholine, Knock-Out mice, HPLC-MS, IQNB, FP-TZTP
Current Pharmaceutical Design
Title: Imaging of Muscarinic Receptors in the Central Nervous System
Volume: 12 Issue: 30
Author(s): W. C. Eckelman
Affiliation:
Keywords: Muscarinic receptor, acetylcholine, Knock-Out mice, HPLC-MS, IQNB, FP-TZTP
Abstract: The development of receptor-binding radiotracers has evolved from a goal of high affinity compounds to give high target to non target ratios to compounds of slightly lesser affinity so that they can reach either steady state after bolus injection or equilibrium after infusion. The other important advance is the ability to measure endogenous neurotransmitter, using various lower affinity muscarinic acetylcholine receptor radioligands. There have been a number of clinical studies that elucidated the mechanism of action of new pharmaceuticals in vivo using external imaging. These include studies of drug interaction of olanzapine, risperidone, clozapine, donepezil, and phenserine with the muscarinic receptor. There have been fewer studies monitoring the effect of therapy in Alzheimers disease, but those pilot studies give great hope that monitoring therapy is a real possibility. Radioligands for the muscarinic receptor, for ACh esterase, and to measure the concentration of acetylcholine have now been developed, A number of studies in small populations have identified changes in mild to moderate Alzheimers disease and, perhaps more importantly, changes in radioligand binding have been identified in clinically normal subjects genetically predisposed to Alzheimers disease by virtue of the epsilon 4+ variant of the APOE gene. Large scale clinical studies are now needed to delineate the true value of these radiotracers in clinical situations. PET and SPECT imaging hold the promise of monitoring the effect of pharmaceuticals in a wide variety of diseases using non-invasive external imaging of the muscarinic cholinergic system.
Export Options
About this article
Cite this article as:
Eckelman W. C., Imaging of Muscarinic Receptors in the Central Nervous System, Current Pharmaceutical Design 2006; 12 (30) . https://dx.doi.org/10.2174/138161206778559678
DOI https://dx.doi.org/10.2174/138161206778559678 |
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
-
Environment, Physical Activity, and Neurogenesis: Implications for Prevention and Treatment of Alzhemiers Disease
Current Alzheimer Research Tuning and Fine-Tuning of Synapses with Adenosine
Current Neuropharmacology Kynurenines in the Central Nervous System: Recent Developments
Central Nervous System Agents in Medicinal Chemistry Computational Studies of Molecular Targets Regarding the Adverse Effects of Isoniazid Drug for Tuberculosis
Current Pharmacogenomics and Personalized Medicine Recent Development in Neuronal Migration Disorders: Clinical, Neuroradiologic and Genetics Aspects
Current Pediatric Reviews Psychotropics and Methadone in Acquired Long QT Syndrome
Current Psychopharmacology Sympathetic Nervous System Dysfunction in Multiple Sclerosis, Linking Neurodegeneration to a Reduced Response to Therapy
Current Pharmaceutical Design Antiepileptics and the Treatment of Neuropathic Pain: Evidence from Animal Models
Current Pharmaceutical Design The Safety, Tolerability, Pharmacokinetics and Cognitive Effects of GSK239512, a Selective Histamine H<sub>3</sub> Receptor Antagonist in Patients with Mild to Moderate Alzheimer’s Disease: A Preliminary Investigation
Current Alzheimer Research Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats
Current Neurovascular Research Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders
CNS & Neurological Disorders - Drug Targets Imaging Biomarkers of Anti-Epileptic Drug Action: Insights from Magnetic Resonance Imaging
Current Pharmaceutical Design Protein Kinases and their Modulation in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Targeting CNS Transporters for Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Cognitive Dysfunction in Major Depressive Disorder: A State-of-the-Art Clinical Review
CNS & Neurological Disorders - Drug Targets Abnormalities of Cortical Thickness in Pediatric Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
Current Medical Imaging Characterization of Single Nucleotide Polymorphisms of Cytochrome P450 in an Australian Deceased Sample
Current Drug Metabolism Development and Optimization of Controlled Porosity Osmotic Tablets of Lamotrigine Solid Dispersion
Recent Patents on Drug Delivery & Formulation Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and <i>Cassia fistula</i> Seed Gum by QbD Approach
Current Drug Delivery Therapeutic Strategy of Erythropoietin in Neurological Disorders
CNS & Neurological Disorders - Drug Targets