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Neuropsychopharmacology: A Tribute to Joseph T. Coyle - 1st Edition - ISBN: 9780128097458, 9780128098202

Neuropsychopharmacology: A Tribute to Joseph T. Coyle, Volume 76

1st Edition

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Serial Volume Editor: Robert Schwarcz
Hardcover ISBN: 9780128097458
eBook ISBN: 9780128098202
Imprint: Academic Press
Published Date: 7th June 2016
Page Count: 414
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Table of Contents

  • Foreword
  • Preface
  • Chapter One: My Life in Clinical Neuroscience: The Beginning
    • Abstract
    • 1 Introduction
    • 2 The Early Years
    • 3 Medical School
    • 4 Postgraduate Training
    • 5 Getting Started at Hopkins
    • 6 Conclusion
  • Chapter Two: Kynurenines and Glutamate: Multiple Links and Therapeutic Implications
    • Abstract
    • 1 Introduction
    • 2 Neurobiology of Kynurenines: The Early Years
    • 3 Kynurenergic Modulation of Glutamate Function: Several Distinct Mechanisms
    • 4 Targeting Kynurenines to Target Glutamate
    • 5 Functional Implications and Clinical Relevance
    • 6 Conclusion
    • Conflict of Interest
    • Acknowledgments
  • Chapter Three: The Therapeutic Role of d-Cycloserine in Schizophrenia
    • Abstract
    • 1 Introduction
    • 2 A Brief Review of NMDA Receptor Structure and Function
    • 3 History of the Glutamate Model of Schizophrenia
    • 4 Glycine-Site Agonists
    • 5 Early Trials with DCS
    • 6 DCS Added to Second-Generation Antipsychotics
    • 7 Glycine Reuptake Inhibitors
    • 8 d-Serine as a Therapeutic Target
    • 9 Inhibitors of Glutamate Release
    • 10 DCS Pharmacology and NMDA Receptor Subunit Composition
    • 11 DCS Memory Enhancing Effects
    • 12 DCS Effects on Memory in Humans
    • 13 NMDA Receptors and Neuroplasticity
    • 14 DCS and Plasticity
    • 15 DCS and Plasticity in Schizophrenia
    • 16 Conclusion
    • Conflict of Interest
  • Chapter Four: Impulsivity, Stimulant Abuse, and Dopamine Receptor Signaling
    • Abstract
    • 1 Introduction
    • 2 Impulsivity as a Therapeutic Target in Stimulant-Use Disorder
    • 3 Dopamine Receptor Signaling and Inhibitory Control
    • 4 Dopamine D2-Type Receptor Deficits and Impulsivity in Stimulant-Use Disorder
    • 5 Augmenting Dopamine Function in Stimulant Users
    • 6 Conclusion
    • Conflict of Interest
  • Chapter Five: Excitotoxicity as a Common Mechanism for Fetal Neuronal Injury with Hypoxia and Intrauterine Inflammation
    • Abstract
    • 1 Introduction
    • 2 Excitotoxicity Mechanisms
    • 3 Hypoxia and Intrauterine Inflammation as a Function of Excitotoxicity in Animal Models
    • 4 Clinical Studies
    • 5 Conclusion
    • Conflicts of Interest
    • Acknowledgments
  • Chapter Six: Transcriptional Regulation of Glutamate Transporters: From Extracellular Signals to Transcription Factors
    • Abstract
    • 1 Introduction
    • 2 Differential Localization of Glutamate Transporters
    • 3 Why Study Transcriptional Regulation of Glutamate Transporters?
    • 4 Conclusion
    • Conflict of Interest
    • Acknowledgments
  • Chapter Seven: The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors
    • Abstract
    • 1 Baltimore, Hopkins, The Coyle Lab, and All that Jazz …
    • 2 Toward Gene Therapy for Brain Tumors: Reengineering the Brain Immune System
    • 3 Conclusions
    • Conflict of Interest
  • Chapter Eight: Choline on the Move: Perspectives on the Molecular Physiology and Pharmacology of the Presynaptic Choline Transporter
    • Abstract
    • 1 Introduction
    • 2 ACh, HACU, and the Birth of CHT
    • 3 CHT Molecular Biology and Regulation
    • 4 CHT Contributions to Cholinergic Function and Dysfunction In Vivo
    • 5 Advances in CHT Pharmacology
    • 6 Conclusion
    • Conflicts of Interest
    • Acknowledgments
  • Chapter Nine: Still NAAG’ing After All These Years: The Continuing Pursuit of GCPII Inhibitors
    • Abstract
    • 1 Introduction
    • 2 Design of GCPII Inhibitors
    • 3 Therapeutic Utility of GCPII Inhibitors in CNS and PNS Disorders
    • 4 Conclusion
    • Conflict of Interest
    • Acknowledgments
  • Chapter Ten: Ultimate Translation: Developing Therapeutics Targeting on N-Methyl-d-Aspartate Receptor
    • Abstract
    • 1 Introduction
    • 2 Neurotransmitters for NMDAR
    • 3 Presynaptic Regulation
    • 4 Postsynaptic Regulation
    • 5 Termination of the Action by d-Amino Acid Oxidase
    • 6 Experiences in CNS Disorders
    • 7 Conclusion
    • Conflict of Interest
    • Acknowledgments
  • Chapter Eleven: The Good and Bad Sides of NAAG
    • Abstract
    • 1 Introduction
    • 2 The History of NAAG
    • 3 NAAG and the Glutamatergic System
    • 4 NMDA Receptors
    • 5 Clinical Implications of NAAG
    • 6 Why is There so Much Controversy Regarding the Effect of NAAG on NMDA Receptors?
    • 7 The Effect of NAAG on NMDA Receptors is Subunit and pH Dependent
    • 8 Possible Mechanism of Action of NAAG on NMDA Receptors
    • 9 Putative Mechanism for NAAG-Mediated Neuroprotection
    • Conflict of Interest
  • Chapter Twelve: The NMDA Receptor and Schizophrenia: From Pathophysiology to Treatment
    • Abstract
    • 1 Introduction
    • 2 NMDA Receptor: Structure and Function
    • 3 Glycine Modulatory Site
    • 4 NMDA Receptor Hypofunction and Schizophrenia
    • 5 Augmenting NMDA Receptor Function to Treat Schizophrenia
    • 6 Conclusion
    • Conflict of Interest
    • Acknowledgments
  • Index


Neuropsychopharmacology: A Tribute to Joseph T. Coyle is a new volume from Advances in Pharmacology presenting reviews of recent breakthroughs in glutamate pharmacology and a tribute to one of the most influential neuroscientists of our times. With a variety of chapters and the best authors in the field, the volume is an essential resource for pharmacologists, immunologists, and biochemists alike.

Key Features

  • Features contributions from the best authors in the field
  • Provides an essential resource for pharmacologists, immunologists, and biochemists
  • Includes new approaches for diagnosing and treating major neurological and psychiatric diseases
  • Features a tribute to one of the most influential neuroscientists of our times


Pharmacologists, immunologists, and biochemists


No. of pages:
© Academic Press 2016
7th June 2016
Academic Press
Hardcover ISBN:
eBook ISBN:


Praise for the Series:
"...recommended not only to pharmacologists but also to all those in related disciplines" --Nature

Ratings and Reviews

About the Serial Volume Editor

Robert Schwarcz

Robert Schwarcz

Dr. Robert Schwarcz is Professor of Psychiatry, Pharmacology and Pediatrics, Director of the NIMH Conte Center for Translational Research, and Head of Neuroscience, Maryland Psychiatric Research Center, at the University of Maryland School of Medicine. After receiving his PhD degree in Biochemistry from the University of Vienna, Austria, he showed in the 1970s, under the mentorship of Dr. Coyle, that an intrastriatal injection of the excitatory amino acid kainate provides an animal model for Huntington's disease. This led to the idea that excitotoxic processes, triggered by an overstimulation of excitatory amino acid receptors, are causally involved in the pathophysiology of several major neurological diseases.

As an offshoot of the excitotoxic hypothesis, Dr. Schwarcz developed the concept and demonstrated that antagonists of excitatory amino acid ("glutamate") receptors prevent or arrest neurodegeneration and hold promise as novel therapeutic agents for major brain diseases. This eventually led to the establishment of anti-excitotoxin-based drug discovery programs in a large number of pharmaceutical houses throughout the world.

More recently, most of Dr. Schwarcz’ work has been concerned with the neurobiology of quinolinate (QUIN) and kynurenate (KYNA), two metabolically related brain constituents with neuroexcitatory (and excitotoxic) and neuroinhibitory (and neuroprotective) properties, respectively. Both QUIN and KYNA are products of the kynurenine pathway of tryptophan degradation. Using a combination of biochemical, histological, behavioral and electrophysiological techniques, he elaborated many of the characteristics and control mechanisms which govern the function of QUIN and KYNA in the brain. Ongoing in vivo and in vitro studies are designed 1) to identify possible abnormalities in kynurenine pathway metabolism in Huntington’s disease, schizophrenia and depression, and in relevant animal models; 2) to further define the neurobiology of QUIN and KYNA by manipulating the kynurenine pathway pharmacologically and genetically; and 3) to develop and use novel kynurenergic drugs in order to normalize functional impairments in the central nervous system.

Dr. Schwarcz has published over 300 peer-reviewed manuscripts and received several major national and international awards and honors, including election as Foreign Professor of the Karolinska Institute in Stockholm in 2009.

Affiliations and Expertise

Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA