Download or read book Ex Vivo Binding of the Agonist PET Radiotracer carbon 11 PHNO to Dopamine D2 D3 Receptors in Rat Brain Lack of Correspondence to the D2 Receptor Two affinity state Model written by Patrick Neil McCormick and published by . This book was released on 2010 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: The dopamine D2 receptor exists in vitro in two states of agonist affinity: a high-affinity state mediating dopamine's physiological effects, and a physiologically-inert low-affinity state. Our primary goal was to determine the in vivo relevance of this two-affinity-state model for the agonist PET radiotracer [11C]-(+)-PHNO, developed for measurement of the D2 high-affinity state. Our second goal was to characterize the regional D2 versus D3 pharmacology of [3H]-(+)-PHNO binding and assess its utility for measuring drug occupancy at both receptor subtypes.Using ex vivo dual-radiotracer experiments in conscious rats, we showed that, contrary to the two-affinity-state model, the binding of [11C]-(+)-PHNO and the antagonist [3H]-raclopride were indistinguishably inhibited by D2 partial agonist (aripiprazole), indirect agonist (amphetamine) and full agonist ((-)-NPA) pretreatment. Furthermore, ex vivo [11C]-(+)-PHNO binding was unaffected by treatments that increase in vitro high-affinity state density (chronic amphetamine, ethanol-withdrawal), whereas unilateral 6-OHDA lesion, which increases total D2 receptor expression, similarly increased the ex vivo binding of [11C]-(+)-PHNO and [3H]- raclopride. These results do not support the in vivo validity of the two-affinity-state model, suggesting instead a single receptor state for [11C]-(+)-PHNO and [3H]-raclopride in conscious rat. Importantly, we also demonstrated that the increased amphetamine-sensitivity of the agonist radiotracers [11C]-(+)-PHNO and [11C]-(-)-NPA, commonly seen in isoflurane-anaesthetized animals and cited as evidence for the two-affinity-state model, is due to the confounding effects of anaesthesia.Using in vitro and ex vivo autoradiography in rat and the D3 receptor-selective drug SB277011, we found that [ 3H]-(+)-PHNO binding in striatum and cerebellum lobes 9 and 10 was due exclusively to D2 and D3 receptor binding, respectively, but in other extra-striatal regions to a mix of the two receptor subtypes. Surprisingly, the D3 contribution to [3H]-(+)-PHNO binding was greater ex vivo than in vitro. Also surprising, several antipsychotic drugs, at doses producing 80% D2 occupancy, produced insignificant (olanzapine, risperidone, haloperidol) or small (clozapine, ∼35%) D3 occupancy, despite similarly occupying both receptor subtypes in vitro. These data reveal a significant discrepancy between in vitro and ex vivo measures of dopamine receptor binding and suggest that the D3 occupancy is not necessary for the therapeutic effect of antipsychotic drugs.
Download or read book Ex Vivo Binding of the Agonist PET Radiotracer 11C PHNO to Dopamine D2 D3 Receptors in Rat Brain written by Patrick N. McCormick and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Pre clinical Evaluation of carbon 11 PHNO as an Agonist Positron Emission Tomography PET Radiotracer for Imaging of the High affinity State of the Dopamine D2 Receptor written by Patrick Neil McCormick and published by . This book was released on 2006 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: In vivo imaging of the D2 receptor with agonist radiotracers could provide important information on the high-affinity, functional state of the D2 receptor in schizophrenia and Parkinson's disease. Here the D2 agonist [11C]-(+)-PHNO was evaluated for use as an agonist PET radiotracer. In vitro, (+)-PHNO was shown, through competitive binding experiments and functional assays for D2 agonism, to be a potent full agonist at the D2 receptor. Ex vivo in rats, [11C]-(+)-PHNO readily crossed the blood-brain barrier and accumulated preferentially in the D2-rich striatum. [11C]-(+)-PHNO pharmacokinetics were rapid, with peak accumulation 5 min after tail-vein injection. The striatal binding of [11C]-(+)-PHNO was highly stereo selective, saturable, had pharmacology appropriate for D2 receptor binding and was sensitive to both increases and decreases in the concentration of endogenous dopamine. These characteristics make [11C]-(+)-PHNO a promising candidate for in vivo imaging of the high-affinity, functional state of the D2 receptor in humans using PET.
Download or read book Estimating Endogenous Dopamine at D2 and D3 Receptors in the Human Brain Using the Agonist Radiotracer 11C PHNO written by Fernando Caravaggio and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cyclin Dependent Kinase 5 Cdk5 written by Nancy Y. Ip and published by Springer Science & Business Media. This book was released on 2009-02-28 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.
Download or read book Novel Antischizophrenia Treatments written by Mark A. Geyer and published by Springer Science & Business Media. This book was released on 2012-10-01 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume tries to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. The volume concentrates on reviewing the ongoing research attempting to identify novel treatments for the cognitive deficits and negative symptoms of schizophrenia, which are not treated adequately by current antipsychotic medications.
Download or read book Methods in Neurotransmitter Receptor Analysis written by Henry I. Yamamura and published by Raven Press (ID). This book was released on 1990 with total page 298 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Trends on the Role of PET in Drug Development written by Philip H. Elsinga and published by World Scientific. This book was released on 2012 with total page 799 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug development is very expensive and a fight against time. PET offers possibilities to speed up this process by adding unique in vivo information on pharmacokinetics/dynamics of a drug at an early stage. This information can help decision makers to move the drug in the drug development process or to decide to stop further developments. This unique and complete book highlights the different ways PET can be used and describes the latest trends in the various disciplines within nuclear medicine to further improve methodologies and increase the number of tools to accelerate drug development. Various topics within tracer development, instrumentation, data analysis and many clinical and preclinical topics are described by leading scientists from industry and academia.
Download or read book Ketamine written by David T. Yew and published by CRC Press. This book was released on 2015-03-16 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: Increasing use of ketamine as a recreational drug in Asia, Europe, and America is a great burden on society at large, leading to aspirational strain, unemployment, and crime. These societal effects have led to growing interest among researchers and clinicians in ketamine's effects on various systems of the body. Ketamine: Use and Abuse reviews the
Download or read book Clinical Nuclear Medicine written by Hans-Jürgen Biersack and published by Springer Science & Business Media. This book was released on 2008-01-03 with total page 573 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work has true international scope, being a unique European/American joint venture that focuses on the state of the art in both diagnostic and therapeutic radionuclide methodology. Pertinent clinical applications are emphasized rather than attempting to cover everything included in the several large comprehensive texts available in our field. This "practical" approach should make it an essential guide to nuclear medicine physicians, technologists, students and interested clinicians alike.
Download or read book Functional Cerebral SPECT and PET Imaging written by Ronald L. Van Heertum and published by Lippincott Williams & Wilkins. This book was released on 2013-04-09 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Fourth Edition reflects the significant recent progress that has occurred in functional brain imaging, particularly the increased use of PET/SPECT, the use of SPECT and PET in movement disorders and dementia, and advances in radiopharmaceutical development and instrumentation. Chapter topics include PET physics and instrumentation, PET radiopharmaceuticals, SPECT radiopharmaceuticals, and technical factors. The entire book has been thoroughly revised to reflect an appropriate balance between SPECT and PET applications. Highlights of this edition include a new chapter on neuroreceptor imaging and kinetic modeling, a new chapter on brain imaging in movement disorders, and significant updates on SPECT radiopharmaceuticals.
Download or read book The Handbook of Radiopharmaceuticals written by Azuwuike Owunwanne and published by Springer. This book was released on 2012-12-06 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: One Radiobiopharmaceutics.- 1 Preparation of radiopharmaceuticals.- Production of radionuclides.- Synthesis of the non-radioactive compound.- Reaction of the radionuclide with the non-radioactive compound.- References.- 2 Ideal characteristics of radiopharmaceuticals.- Availability and cost.- Preparation.- Biologic behavior.- Radionuclidic characteristics.- Hematology.- 3 Quality control of radiopharmaceuticals.- Biologic tests.- Physicochemical tests.- References.- 4 Design of radiopharmaceuticals.- Radionuclide.- Chemistry.- Biology.- Human studies.- Registration.- References.- 5 The fate of.
Download or read book Quantitative Functional Brain Imaging with Positron Emission Tomography written by Richard E. Carson and published by Elsevier. This book was released on 1998-09-08 with total page 535 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the latest scientific developments in the field of positron emission tomography (PET) dealing with data acquisition, image processing, applications, statistical analysis, tracer development, parameter estimation, and kinetic modeling. It covers improved methodology and the application of existing techniques to new areas. The text also describes new approaches in scanner design and image processing, and the latest techniques for modeling and statistical analyses. This volume will be a useful reference for the active brain PET scientist, as well as a valuable introduction for students and researchers who wish to take advantage of the capabilities of PET to study the normal and diseased brain. Authored by international authorities in PET Provides the latest up-to-date techniques and applications Covers all fundamental disciplines of PET in one volume A comprehensive resource for students, clinicians, and new PET researchers
Download or read book Sigma Receptors written by Rae R. Matsumoto and published by Springer Science & Business Media. This book was released on 2007-02-15 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an update on sigma receptors, and summarizes recent advances in the medicinal chemistry, molecular biology, and cell biology of sigma receptors. It describes the functional effects mediated by these receptors and the potential clinical implications of these actions. The information is put in a historical perspective. This provides a launching point from which future studies and research directions can easily be developed.
Download or read book Cognitive Neuroscience of Aging written by Roberto Cabeza and published by Oxford University Press. This book was released on 2017 with total page 633 pages. Available in PDF, EPUB and Kindle. Book excerpt: A rapidly growing body of research has consituted a new discipline that may be called cognitive neuroscience of aging. This book offers an introduction to the topic, useful to both professionals & students in cognitive neuroscience, cognitive psychology, neuroscience, neuropsychology & neurology.
Download or read book PET and SPECT in Psychiatry written by Rudi A.J.O. Dierckx and published by Springer Science & Business Media. This book was released on 2014-03-28 with total page 851 pages. Available in PDF, EPUB and Kindle. Book excerpt: PET and SPECT in Psychiatry showcases the combined expertise of renowned authors whose dedication to the investigation of psychiatric disease through nuclear medicine technology has achieved international recognition. The classical psychiatric disorders as well as other subjects – such as suicide, sleep, eating disorders, and autism – are discussed and the latest results in functional neuroimaging are detailed. Most chapters are written jointly by a clinical psychiatrist and a nuclear medicine expert to ensure a multidisciplinary approach. This state of the art compendium will be valuable to all who have an interest in the field of neuroscience, from the psychiatrist and the radiologist/nuclear medicine specialist to the interested general practitioner and cognitive psychologist. It is the first volume of a trilogy on PET and SPECT imaging in the neurosciences; other volumes will focus on PET and SPECT in neurology and PET and SPECT of neurobiological systems.
Download or read book Peripheral Benzodiazepine Receptors written by Eva Giesen-Crouse and published by Academic Press. This book was released on 1993-05-05 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences. Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas. Although peripheral type benzodiazepne recognition sites have been demonstrated in the brain and peripheral organs of various species for more than 10 years, the exact physiological function or pharmacological effects have not yet been established. Peripheral benzodiazepine literature is so overwhelming that the novice may find it virtually impossible to form a clear idea about the diverse findings. This volume, dedicated exclusively to pBR and their natural and synthetic ligands, puts the available data into perspective. A truly interdisciplinary approach has brought neuroscientists, cardiologists, endocrinologists, and immunologists together to work on the description of pBR-mediated effects. The chemistry, biochemistry, and molecular biology of the pBR receptor and its ligands are reviewed, their pharmacological usefulness is conjectured, and thus a true overview of the field is provided. * SPECIAL FEATURES * This volume follows the Neuroscience Perspectives brief of providing a historical background, pharmacological, biochemical and physiological aspects of research and therapeutic potential, of its chosen topic. * The peripheral benzodiazepine recognition site has been recognised for more than ten years, but the exact physiological and pharmacological effects have not yet been established.
