Adenosine Receptors and Parkinson's Disease
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Table of contents
- Adenosine Receptors and Parkinson's Diseaseiii
- Copyright Pageiv
- Contentsv
- Contributorsxiii
- Prefacexvii
- Chapter 1. Introductory Remarks: Adenosine A2A Receptor Antagonists: A Novel Approach to the Treatme1
- I. A View of the Action of Adenosine in the Striatum5
- References13
- Chapter 2. Localization of Adenosine Receptors in Brain and Periphery17
- I. Adenosine17
- II. Receptor Subtypes18
- III. Summary27
- References27
- Chapter 3. Medicinal Chemistry of Adenosine Receptors in Brain and Periphery31
- I. Introduction31
- II. A1 Adenosine Receptor Antagonists32
- III. A2A Adenosine Receptor Antagonists36
- IV. Conclusion42
- References43
- Chapter 4. Overview of the Physiology and Pharmacology of Adenosine in the Peripheral System49
- I. Metabolism, Receptors, and Modulation of Adenosine51
- II. Peripheral Nervous System54
- III. Cardiovascular System55
- IV. Renal Effects58
- V. Respiratory and Pulmonary System60
- VI. Gastrointestinal System62
- VII. Inflammation and Immune System63
- VIII. Endocrine and Exocrine Effects65
- IX. Concluding Remarks67
- References67
- Chapter 5. Biochemical Characterization of Adenosine Agonists and Antagonists77
- I. Introduction77
- II. Ligands for Adenosine Receptor Subtypes78
- III. Signal Transduction89
- IV. Biochemical Basis of the Use of A2A Antagonists in Parkinson’s Disease96
- V. Conclusion99
- References99
- Chapter 6. Physiology of Adenosine Receptors in the Striatum107
- I. Introduction107
- II. Striatal Cell Subtypes108
- III. The Striatal Medium Spiny Neurons109
- IV. A2A Receptor-Mediated Suppression of GABAergic Transmission onto Medium Spiny Neurons110
- V. Adenosine Receptor Modulation of Glutamatergic Synaptic Transmission in the Striatum117
- VI. Influence of Adenosine Receptor Activation on Membrane Properties of Medium Spiny Neurons118
- VII. Antiparkinsonian Effects of A2A Receptor Antagonists119
- VIII. Conclusion123
- References124
- Chapter 7. Regulation of Neurotransmitter Release in Basal Ganglia by Adenosine Receptor Agonists an129
- I. Introduction129
- II. Methodology130
- III. The Adenosine A1 Receptor in the Basal Ganglia132
- IV. The Adenosine A2 Receptors in the Basal Ganglia136
- V. Relevance of the A2A Receptor to the Therapy of Parkinson’s Disease142
- References144
- Chapter 8. Control of Gene Expression in Basal Ganglia by Adenosine Receptors149
- I. Introduction149
- II. Effect of CGS15943A on Proenkephalin mRNA Levels in Dopamine-Depleted Striatum153
- III. Effect of A2 and A1 Adenosine Receptor Antagonism on Levels of Striatal Peptide Gene Expression157
- IV. Discussion162
- References167
- Chapter 9. Knockout Mice in the Study of Dopaminergic Diseases171
- I. Introduction171
- II. D2-like Receptors173
- III. D1-like Receptors177
- IV. Dopamine D1 and D2 Receptor Interactions in Basal Ganglia178
- V. Dopamine and Adenosine180
- VI. D2 Receptor-Deficient Mice182
- VII. Adenosine A2A Receptor-Deficient Mice185
- VIII. Animal Models of Neuropathologies: D2 Receptor-Deficient Mice and Parkinson’s Disease185
- References186
- Chapter 10. Effects of Adenosine Receptors193
- I. Introduction193
- II. The Role of Adenosine A1 Receptor in the CNS in Cognition194
- III. Role of Adenosine A2A Receptor in CNS199
- IV. Conclusion205
- V. Methods205
- Acknowledgments207
- References207
- Chapter 11. Actions of Adenosine Antagonists in Primate Model of Parkinson’s Disease211
- I. Introduction211
- II. Action of MPTP on Motor Behavior in Common Marmosets212
- III. Effects of Adenosine Receptor Ligands on Motor Dysfunction in MPTP-Treated Common Marmosets214
- IV. Effect of Adenosine A2A Receptor Antagonist KW-6002 on L-Dopa-Induced Dyskinesias219
- V. Effect of Chronic Administration of Adenosine A2A Receptor Antagonist KW-6002221
- VI. Comparison of the Antiparkinsonian Activity of L-Dopa and AZA Antagonist KW-6002222
- VII. Conclusion224
- Acknowledgments225
- References225
- Chapter 12. Selective Adenosine A2A Receptor Antagonism as an Alternative Therapy for Parkinson’s229
- I. Introduction229
- II. Materials and Methods232
- III. Results234
- IV. Discussion236
- V. Conclusion240
- References240
- Chapter 13. Neurobiology of Adenosine Receptors245
- I. Introduction245
- Chapter 14. The Relevance of Adenosine A2A Antagonists to the Treatment of Parkinson’s Disease: Co257
- Introduction257
- Striatal Output Pathways and Parkinson’s Disease259
- Alterations in Striatal Output Pathways Following the Occurrence of Dyskinesia260
- Final Comments261
- Acknowledgments262
- References262
- Index265
- Color Plate SectionColor Plate-1
This book is the first definitive overview on adenosine receptor antagonists and their application to the treatment of Parkinson's Disease. The effect of these novel non-dopamine drugs on vitro and in vivo systems clearly shows their potential for the treatment of this debilitating disease. This book covers how the Parkinson's disease antagonist drug, A2A, has been researched, developed, and tested. It is an essential book for researchers interested in the basal ganglia, purine biology, and Parkinson's Disease.
Key Features
* Discusses the discovery and development of a novel non-dopaminomimetic agent for Parkinson's disease
* Provides the first definitive overview of adenosine antagonists and their role in the treatment of Parkinson's disease
* Presents a new mechanism of action of adenosine A2A receptor antagonists in motor function
Proposes a hypothesis of adenosine A2A receptor function in the striatum
* Comprehensive overview of adenosine, its receptor subtypes, their antagonists/agonists from biochemistry, molecular biology, medicinal chemistry, physiology, pharmacology, and neurochemistry viewpoints
Key Features
* Discusses the discovery and development of a novel non-dopaminomimetic agent for Parkinson's disease
* Provides the first definitive overview of adenosine antagonists and their role in the treatment of Parkinson's disease
* Presents a new mechanism of action of adenosine A2A receptor antagonists in motor function
Proposes a hypothesis of adenosine A2A receptor function in the striatum
* Comprehensive overview of adenosine, its receptor subtypes, their antagonists/agonists from biochemistry, molecular biology, medicinal chemistry, physiology, pharmacology, and neurochemistry viewpoints