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Front Cover
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Phosphodiesterase Inhibitors
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Copyright Page
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Contents
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Contributors
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Series Preface
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Preface
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Chapter 1. Identification and Quantification of PDE Isoenzymes and Subtypes by Molecular BiologicaI Methods
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1. Introduction
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2. The PDE Gene Family
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3. Molecular Cloning and Localization of the Mammalian PDEs
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4. Summary
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5. References
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Chapter 2. Analysis of PDE Isoenzyme Profiles in Cells and Tissues by Pharmacological Methods
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1. Introduction
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2. Analysis of PDE Isoenzyme Activities in Cells and Tissues
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3. Regulation of PDE Isoenzyme Activities
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4. Conclusions
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5. References
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Chapter 3. Effects of Theophylline and Non-selective Xanthine Derivatives on PDE Isoenzymes and Cellular Function
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1. Introduction
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2. Inhibition of PDE
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3. Effects on Cell Function
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4. Summary and Directions for Future Research
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5. References
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Chapter 4. Ca 2+/Calmodulin-dependent Cyclic Nucleotide Phosphodiesterase (PDE1)
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1. Introduction
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2. Purification and Characterization
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3. Isoenzymes of CaM-PDE
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4. Activity in Cancer Cells
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5. Conclusions
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6. Acknowledgements
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7. References
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Chapter 5. EHNA as an Inhibitor of PDE2: a Pharmacological and Biochemical Study in Cardiac Myocytes
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1. Introduction
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2. Methods
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3. Results
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4. Discussion
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5. Acknowledgements
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6. References
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Chapter 6. cGMP-Inhibited Phosphodiesterases (PDE3)
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1. Introduction
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2. Purification and Characterization
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3. Molecular Cloning and Domain Organization
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4. Structure/Function Relationships
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5. Pharmacology and Potential Therapeutic Usage of PDE3 Inhibitors
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6. Therapeutic Usage of PDE3 Inhibitors
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7. Acknowledgements
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8. References
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Chapter 7. Interaction of PDE4 Inhibitors with Enzymes and Cell Functions
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1. The PDE4 Isoenzyme Family
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2. Pharmacology of PDE4 Inhibitors
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3. Adverse Effects of PDE4 Inhibitors
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4. PDE4 Alterations in Allergic Diseases
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5. Summary and Future Directions
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6. References
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Chapter 8. Inhibition of Phosphodiesterase Isoenzymes and Cell Function by Selective PDE5 Inhibitors
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1. Introduction
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2. Scientific Rationale for PDE5 Inhibitors
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3. PDE5 Inhibition and Vasorelaxation
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4. Potential Therapeutic Applications of PDE5 Inhibitors
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5. Additional Indications for PDE5 Inhibitors
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6. Newer PDE5 Inhibitors
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7. Combination Inhibitors
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8. Summary
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9. Acknowledgement
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10. References
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Chapter 9. Design and Synthesis of Xanthines and Cyclic GMP Analogues as Potent Inhibitors of PDE5
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1. Introduction
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2. Strategy for the Design of PDE5 Inhibitors
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3. Synthesis of IBMX and cGMP Analogues as PDE Inhibitors
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4. Selectivity of the IBMX Analogues as PDE Inhibitors
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5. cGMP Analogues as PDE Inhibitors
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6. Smooth Muscle Relaxation by IBMX and cGMP Analogues
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7. Conclusions
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8. Acknowledgements
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9. References
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Chapter 10. Enzymatic and Functional Aspects of Dual-selective PDE3/4 Inhibitors
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1. Introduction
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2. Dual Inhibitors of PDE3/4 for Asthma Therapy
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3. Preclinical Pharmacology of PDE3/4 Inhibitors
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4. Clinical Experience with PDE3/4 Inhibitors
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5. Conclusions
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6. References
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Chapter 11. An Isoform-selective Inhibitor of Cyclic AMP-specific Phosphodiesterase (PDE4) with Anti-inflammatory Properties
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1. Introduction
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2. Materials and Methods
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3. Results
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4. Discussion
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5. Acknowledgements
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6. References
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Chapter 12. Characterization of Different States of PDE4 by Rolipram and RP 73401
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1. Introduction
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2. Pharmacology of RP 73401
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3. Interactions of RP 73401 and Rolipram with Eosinophil PDE4
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4. Inhibition of PDE4 from Other Cells and Tissues
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5. Possible Therapeutic Implications
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6. Conclusions
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7. References
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Chapter 13. MolecularAspects of Inhibitor Interaction with PDE4
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1. Introduction
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2. Molecular Biology of PDE4
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3. Rolipram-Binding Site
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4. Mechanistic Enzymology
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5. Structure-Activity Relationships
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6. Summary and Conclusions
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7. References
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Glossary
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Key to Illustrations
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Index
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Color Plate Section
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