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دانلود کتاب The Kappa Opioid Receptor

دانلود کتاب گیرنده اپیوئیدی کاپا

The Kappa Opioid Receptor

مشخصات کتاب

The Kappa Opioid Receptor

ویرایش: [1 ed.] 
نویسندگان:   
سری: Handbook of Experimental Pharmacology, 271 
ISBN (شابک) : 3030890732, 9783030890735 
ناشر: Springer 
سال نشر: 2021 
تعداد صفحات: 588
[574] 
زبان: English 
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود) 
حجم فایل: 17 Mb 

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توضیحاتی در مورد کتاب گیرنده اپیوئیدی کاپا

این کتاب آخرین دانش در ساختار، سیگنال دهی و فارماکولوژی بیوشیمیایی KOR و همچنین تحقیقات پیش بالینی و کاربردهای بالینی (شامل مطالعات فاز بالینی و تایید شده برای استفاده انسانی) از ترکیبات KOR را پوشش می دهد. این به سه بخش تقسیم می شود: جنبه های مولکولی KOR، تحقیقات پیش بالینی در مورد فارماکولوژی آگونیست ها و آنتاگونیست های KOR در حیوانات و آگونیست ها و آنتاگونیست های KOR در استفاده بالینی و در آزمایشات بالینی گذشته و حال. فصل‌های «حسگرهای زیستی تأثیرات انتخابی لیگاند را در گیرنده‌های کاپا نظارت می‌کنند» و «نقش دینورفین و گیرنده اپیوئیدی کاپا در اسکیزوفرنی و اختلال افسردگی اساسی: رویکردی ترجمه‌ای» این کتاب با دسترسی آزاد تحت عنوان Creative Commons Attribution 4.0 International در دسترس هستند. مجوز از طریق link.springer.com.


توضیحاتی درمورد کتاب به خارجی

This book covers the latest knowledge in structure, signaling, and biochemical pharmacology of KOR as well as preclinical research and clinical applications (including clinical phase studies and approved for human use) of KOR compounds. It is divided up into the three parts: Molecular aspects of KOR, Preclinical research on pharmacology of KOR agonists and antagonists in animals and KOR agonists and antagonists in clinical use and in past and present clinical trials. The chapters "Biosensors monitor ligand-selective effects at kappa opioid receptors" and "The role of dynorphin and the kappa opioid receptor in schizophrenia and major depressive disorder: a translational approach" of this book are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.



فهرست مطالب

Preface
Contents
Part I: Basics
Fundamentals of the Dynorphins/Kappa Opioid Receptor System: From Distribution to Signaling and Function
	1 Historical Perspectives
	2 Dynorphin Peptides
	3 Cloning of the KOR
	4 Neuroanatomy of the KOR
	5 KOR Signaling at the Cellular Level
	6 Agonist-Promoted KOR Phosphorylation and Regulation
	7 X-ray Crystal Structures of the KOR
	8 In Vivo Pharmacology of the DYNs/KOR System
	9 Conclusion
	References
Considerations on Using Antibodies for Studying the Dynorphins/Kappa Opioid Receptor System
	1 Introduction
	2 General Considerations for Validation of Specificity of Antibodies
		2.1 Unique Issues Associated with Antibodies Against G Protein-Coupled Receptors (GPCRs)
		2.2 Validation of Specificity of Antibodies
	3 Antibodies for IHC of the KOR
		3.1 Characterization of KT2 Antibody and KOR1 Antibodies for IHC
		3.2 IHC of the KOR in the Brain
		3.3 Generation of a Mouse Line Expressing a Fusion Protein of the KOR Conjugated with tdTomato (KOR-tdT)
	4 KOR Antibodies for IB
		4.1 Detection of KOR Expressed in Cells
		4.2 Detection of the KOR in Mouse Brains
	5 Antibodies for IB of Phosphorylated KOR
		5.1 Detection of Phosphorylated KOR in Cells
		5.2 Detection of Phosphorylated KOR in Mouse Brains
		5.3 U50,488H Promoted KOR Phosphorylation at T363 and S369 in Mouse Brains in a Dose-Dependent Manner
	6 KOR Antibodies from Commercial Sources
	7 Antibodies against Dynorphins: Some Considerations
	8 Conclusion
	References
Part II: In Vitro Studies
Structural Characterization of KOR Inactive and Active States for 3D Pharmacology and Drug Discovery
	1 Introduction
	2 Structure Determination of KOR
		2.1 KOR-JDTic Structure in Inactive State
		2.2 KOR-MP1104 Structure in Active State
		2.3 JDTic-KOR-Nb6 Structure in Inactive State
	3 Overall Architecture of the KOR in Inactive and Active States
	4 Structural Determinants of Long-Acting Antagonist JDTic Binding in Inactive Structure
	5 Structural Determinants of Agonist MP1104 Binding in the Active-State Structure
	6 Large-Scale Conformational Changes in KOR as a Part of the Activation Mechanism
	7 Structure-Based Insights into KOR 3D Pharmacology
		7.1 KOR Antagonists: Long-Acting and Short-Acting
		7.2 KOR Agonists
		7.3 Determinants of Opioid Ligand Selectivity at KOR
	8 Applications of KOR Structure to Computer-Assisted Ligand Discovery
		8.1 Understanding KOR Dynamics by MD Simulations
		8.2 Discovery of New KOR Chemotypes by Structure-Based Virtual Screening
		8.3 Rational Design for KOR Selectivity Over MOR and DOR
		8.4 Rational Design for KOR Functional Selectivity
	9 Conclusions and Outlook
	References
Biosensors Monitor Ligand-Selective Effects at Kappa Opioid Receptors
	1 Introduction: Ligand-Selective Effects at the Kappa Opioid Receptor
	2 Nanobodies and Mini-G Proteins Act as Conformation-Specific KOR Binders
		2.1 Active State Binding Nanobodies Nb39 and Nb33
		2.2 Inactive State Binding Nanobody Nb6
		2.3 Active State Binding Mini-G Protein Mini-Gsi
	3 Biosensors Robustly and Rapidly Report on KOR Activation and Deactivation
	4 Biosensors Reveal Ligand-Selective Effects at KOR
		4.1 Ligand-Selective Recruitment of Distinct Biosensors to KOR
		4.2 Agonist-Selective Activation of KOR at Distinct Cellular Locations
	5 Conclusions and Outlook
	References
Does GEC1 Enhance Expression and Forward Trafficking of the Kappa Opioid Receptor (KOR) via Its Ability to Interact with NSF D...
	1 Introduction
	2 Experimental Procedures
		2.1 Pull-Down Assays Using Purified Recombinant Proteins Expressed in E. coli
	3 Results
	4 Discussion
	References
Kappa Opioid Receptor Mediated Differential Regulation of Serotonin and Dopamine Transporters in Mood and Substance Use Disord...
	1 Introduction
	2 KOR and the Serotonergic System
		2.1 KOR Interaction with Serotonergic System and Its Relevance to Psychiatric Disorders
		2.2 KOR Signaling in the Regulation of Serotonin Clearance: Modulation of Serotonin Transporter Function, Trafficking, and Pho...
	3 KOR and the Dopaminergic System
		3.1 KOR Interaction with Dopaminergic System and Its Relevance to Cocaine Use Disorder
		3.2 KOR Signaling in the Regulation of Dopamine Clearance: Modulation of Dopamine Transporter Function and Trafficking
	4 Dynorphin/KOR System as a Therapeutic Target
	5 Conclusions
	References
Part III: Preclinical Drug Development
Biased Ligands at the Kappa Opioid Receptor: Fine-Tuning Receptor Pharmacology
	1 Introduction: Biased Signaling and the Kappa Opioid Receptor
	2 Signaling Cascades Downstream of the Kappa Opioid Receptor
		2.1 G Proteins
		2.2 βarrestin2 Activation
	3 Physiological Implications of Signaling Pathways Downstream of the Kappa Opioid Receptor
	4 Biased Ligands at the Kappa Opioid Receptor
	5 Conclusions
	References
Preclinical Studies on Nalfurafine (TRK-820), a Clinically Used KOR Agonist
	1 Introduction
	2 In Vitro Pharmacological Characterization of Nalfurafine
		2.1 Bioassays
		2.2 Binding Affinity and Selectivity Profile of Nalfurafine at MOR, DOR, KOR and NOR
		2.3 No Significant Binding to Targets Other Than Opioid Receptors
		2.4 Efficacies and Potencies of Nalfurafine in Activating MOR, DOR, KOR and NOR: Inhibition of Adenylate Cyclase and Enhanceme...
		2.5 Functional Selectivity of Nalfurafine in KOR-Mediated Activation of G Proteins and β-Arrestins
		2.6 KOR Internalization and Down-Regulation
	3 In Vivo Pharmacological Effects of Nalfurafine
		3.1 Antipruritic Effects
		3.2 Anti-nociceptive Effects
		3.3 Anti-allodynic and Anti-hyperalgesic Effects
		3.4 Inhibition of Neurogenic Inflammation
		3.5 Aversive Effects or Lack Thereof
		3.6 Effects on Locomotor Activity and Motor Coordination
		3.7 Water Diuretic Effects
		3.8 Nalfurafine and U50,488H Induced Different Phosphoproteomic Changes in Mouse Brains
		3.9 Effect of Nalfurafine on Pharmacological Actions of Morphine
			3.9.1 Effects on Morphine-Induced Itch
			3.9.2 Effect on Morphine-Induced Antinociception
			3.9.3 Effects on Rewarding Properties of Morphine and Oxycodone
			3.9.4 Effects on Morphine-Induced Tolerance and Dependence
			3.9.5 Effects on Morphine-Induced Hyperlocomotion
	4 Nalfurafine as an Abuse-Deterring Agent for Prescription Opioid Abuse
		4.1 Translational Significance of Contingent vs. Non-contingent Administration of KOR Agonists
		4.2 Behavioral Pharmacology of Nalfurafine/Oxycodone Combinations
			4.2.1 Studies in Rats
			4.2.2 Studies in Nonhuman Primates
	5 Effects of Nalfurafine on Alcohol Drinking
		5.1 The Dynorphins/KOR System in Alcohol-Related Behaviors
		5.2 Development of Nalfurafine as a Potential Therapeutic Agent for Alcoholism
	6 Effect of Nalfurafine on CPP and Discriminative Stimulus Effects of Cocaine
	7 Other Effects
	8 Conclusion
	References
Kappa Opioid Receptor Ligands and Pharmacology: Diphenethylamines, a Class of Structurally Distinct, Selective Kappa Opioid Li...
	1 Introduction
	2 KOR Ligands and Their Pharmacology
		2.1 Natural Ligands
		2.2 Synthetic Ligands
		2.3 Diphenethylamines, a New Class of Selective KOR Ligands
			2.3.1 Agonists and Partial Agonists
			2.3.2 Biased Agonists
			2.3.3 Antagonists
			2.3.4 In Vivo Pharmacology
	3 Conclusion
	References
Peptide Kappa Opioid Receptor Ligands and Their Potential for Drug Development
	1 Introduction
		1.1 Actions of the Endogenous Kappa Opioid System and Resultant Potential Therapeutic Applications of Ligands for Kappa Opioid...
		1.2 Review of Key Non-Peptidic Kappa Opioid Receptor-Selective Ligands
	2 Peptide Ligands for Kappa Opioid Receptors
		2.1 Dynorphin A Analogs
		2.2 Tetrapeptide KOR Ligands
			2.2.1 All-D-Amino Acid Peptides
			2.2.2 Endomorphin-1 Derivative
			2.2.3 Macrocyclic Tetrapeptides
	3 Conclusions
	References
Part IV: Preclinical Studies: In Vivo Pharmacology
Dynorphin/Kappa-Opioid Receptor System Modulation of Cortical Circuitry
	1 Introduction
		1.1 Cortical Circuits
		1.2 Anatomy of the Cortical DYN/KOR System
		1.3 Function of the DYN/KOR System in the Cortex
		1.4 Behavioral Effects of the DYN/KOR System in the Cortex
		1.5 Implication for Human Health and Diseases
		1.6 Unknowns and Future Directions for the Field
			1.6.1 DYN/KOR Regulation of Dendritic Integration
			1.6.2 Conservation Across Species
			1.6.3 Site of Psychotomimetic Effects
			1.6.4 Interactions with Other Stress-Related Peptides/Systems
			1.6.5 Novel Approaches to Study the DYN/KOR System
	2 Conclusions
	References
Molecular Genetics of Kappa Opioids in Pain and Itch Sensations
	1 The Kappa Opioid System in Pain
		1.1 Peripheral Effects of Dynorphins (DRG and TG Neurons)
		1.2 Dynorphin Neurons in the Spinal Cord
		1.3 Functions of the Dynorphin/KOR System in the Parabrachial Nucleus
		1.4 Role of Kappa Opioids in Pain-Induced Stress Responses in the Dorsal Raphe Nucleus, Amygdala, Rostral Ventral Medulla, and...
		1.5 Summary and Future Direction of Kappa Signaling in Control of Pain
	2 Kappa Opioids in Itch
		2.1 Dynorphin Spinal Cord Interneurons Inhibit Itch
		2.2 Neuronal Circuits for Itch
		2.3 Summary and Future Direction for Itch Research
	3 Common Mechanisms of Action of the Kappa Opioid System
	References
Antipruritic Effects of Kappa Opioid Receptor Agonists: Evidence from Rodents to Humans
	1 Introduction
	2 A Brief Introduction to the Field of Itch
		2.1 Terminology and Classification of Itch
		2.2 Animal Models of Itch
	3 KORs Are Involved in the Sensation of Itch
		3.1 Kappa Opioid Receptor Antagonists Evoke Scratching in Mice
		3.2 Antipruritic Effects of Kappa Opioid Receptor Agonists Against Different Pruritogens
	4 Conclusions
	References
Antinociceptive Effects of Kappa-Opioid Receptor Agonists
	1 The Difficulty in Assessing Pain with Preclinical Models
	2 KORs and Antinociception in Pain-Stimulated Behaviors
	3 KORs and Antinociception in Pain-Depressed Behaviors
	4 A Biased Future for KOR Agonists
	5 Conclusion
	References
Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction
	1 Introduction
	2 Functional Upregulation of KOR Systems in Chronic Pain States
		2.1 Dynorphin Peptides Can Exacerbate Nociceptive Transmission via Non-opioid Mechanisms
		2.2 Chronic Pain Changes KOR Function and Expression in Supra-Spinal Sites
		2.3 Kappa OR Agonist-Induced Place Aversion Is Enhanced in Chronic Pain States
	3 Kappa OR Modulation of the Affective, Emotional Dimension of Pain
		3.1 Kappa OR Ligands Do Not Alter Acute Pain-Induced Aversion or Depression of ICSS
		3.2 Kappa OR Systems Contribute to Ongoing Persistent Pain States
	4 Is There Potential for KOR Antagonism as a Management Strategy for Chronic Pain-Associated Negative Affect?
	5 Evidence That KOR Systems May Contribute to Drug-Seeking Behavior in Chronic Pain States
	6 Conclusions
	References
KOR Control over Addiction Processing: An Exploration of the Mesolimbic Dopamine Pathway
	1 Introduction
	2 KOR Interactions with the Dopamine System
		2.1 KOR-Mediated Regulation of Dopamine Release
		2.2 KOR-Mediated Regulation of Dopamine Uptake
		2.3 KOR-Mediated Regulation of D2/D3 Receptors
	3 Behavioral Effects of KOR Activation in Humans and Animal Models
	4 Involvement of KOR in Addiction Processing and Stress
		4.1 KOR and Alcohol Use Disorder
		4.2 KOR and Substance Use Disorder
		4.3 Acute and Chronic Stress Impact on Dynorphin/KOR System
		4.4 Stress-Induced Development of Drug Addiction
	5 Conclusion
	References
The Kappa Opioid Receptor System in Temporal Lobe Epilepsy
	1 Introduction
	2 The Hippocampal Formation and Temporal Lobe Epilepsy
		2.1 The Hippocampal Formation
			2.1.1 The Dentate Gyrus
			2.1.2 CA3
			2.1.3 CA1
			2.1.4 Subiculum
	3 The Kappa Opioid Receptor and Dynorphin Expression in the Hippocampal Formation
	4 Kappa Opioid Receptors and the Control of Network Excitability
	5 Alterations of Dynorphins and Kappa Opioid Receptor System in Epilepsy
	6 Kappa Opioid Receptor as a Potential Therapeutic Target
	References
Kappa Opioid Agonist-Induced Diuresis: Characteristics, Mechanisms, and Beyond
	1 Introduction
	2 KOR Agonist-Induced Diuresis
	3 Possible Mechanisms for KOR Agonist-Induced Diuresis
	4 Therapeutic Value of KOR Agonist-Induced Water Diuresis
	5 Conclusions
	References
Kappa Opioid Receptor Expression and Function in Cells of the Immune System
	1 Introduction
	2 Expression of the KOR
	3 Functional Activity of the KOR Expressed by Hematopoietic Cells
		3.1 Antibody Response
		3.2 Phagocytic Activity
		3.3 Cytokine and Cytokine Receptor Expression
			3.3.1 Accessory Cell Cytokine and Cytokine Receptor Expression
			3.3.2 T Cell Cytokine and Cytokine Receptor Expression
			3.3.3 T Cell Development
			3.3.4 Molecular Basis for Regulation of Chemokine Receptor Expression
	4 Cross-Talk Between KOR and CXCR4
	5 Summary
	References
Pleiotropic Effects of Kappa Opioid Receptor-Related Ligands in Non-human Primates
	1 The Dynorphin-Kappa Opioid Receptor System
	2 Effects of Dynorphins in Non-human Primates
	3 Kappa Opioid Receptor Agonists as Antipruritics
		3.1 Systemic Effects
		3.2 Intrathecal Effects
	4 Kappa Opioid Receptor Agonists as Analgesics
		4.1 Centrally Acting Kappa Opioid Receptor Agonists
		4.2 Peripherally Acting Kappa Opioid Receptor Agonists
	5 Kappa Opioid Receptor-Related Ligands for the Treatment of Substance Use Disorders
		5.1 Effects of Kappa Opioid Receptor-Related Agonists
		5.2 Effects of Kappa Opioid Receptor Antagonists
	6 Pleiotropic Effects of Kappa Opioid Receptor-Related Ligands
	7 Conclusion
	References
Part V: Clinical Studies and Concepts
Clinical Profiles of Nalfurafine Hydrochloride for the Treatment of Pruritus Patients
	1 Introduction
	2 Cytochrome P450 Enzymes Involved in Metabolism
	3 Drug-Drug Interactions Involving P-Glycoprotein
	4 Efficacy and Safety in Dialysis Patients with Uremic Pruritus
		4.1 Uremic Pruritus in Hemodialysis Patients
			4.1.1 Efficacy
			4.1.2 Safety
		4.2 Peritoneal Dialysis Patients with Uremic Pruritus
			4.2.1 Efficacy
			4.2.2 Safety
	5 Efficacy and Safety in Chronic Liver Disease Patients with Hepatic Pruritus
		5.1 Hepatic Pruritus in Chronic Liver Disease Patients
			5.1.1 Efficacy
			5.1.2 Safety
	6 Perspectives
	References
Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders
	1 Introduction
	2 Long-Duration KOR Antagonists
		2.1 Nor-Binaltorphimine
		2.2 5′-Guanidinonaltrindole
		2.3 JDTic
	3 Short Duration KOR Antagonists
		3.1 Peptidic Antagonists
		3.2 PF-4455242
		3.3 AZ-MTAB
		3.4 LY2456302: Animal Studies
		3.5 LY2456302: Human Studies
		3.6 LY2444296
		3.7 BTRX-335140
	4 Conclusions
	References
Kappa Opioid Receptors in the Pathology and Treatment of Major Depressive Disorder
	1 Introduction
	2 Literature Search
	3 Clinical Studies
		3.1 Postmortem Studies
		3.2 KOR and DYN as Potential Biomarkers of MDD
		3.3 Aticaprant: NIH Fast Fail Initiative
	4 Preclinical Studies
		4.1 Stress-Induced Changes in Oprk and Pdyn Expression
		4.2 Rescue of Stress-Induced Behavioral Deficits by KOR Antagonists
	5 Conclusion
	References
The Role of Dynorphin and the Kappa Opioid Receptor in Schizophrenia and Major Depressive Disorder: A Translational Approach
	1 Introduction
	2 KOR Agonists in Preclinical Models and Healthy Volunteers
		2.1 Selective KOR Antagonists
		2.2 Nonselective Opioid Antagonists
	3 Therapeutic Targeting of the DYN/KOR System in Schizophrenia
		3.1 Evidence for Abnormal DYN Signaling in Schizophrenia
		3.2 Preclinical Evidence from Selective KOR Agonists
		3.3 Treatment with Nonselective Opioid Antagonists Is Significantly Associated with Reductions in the Symptoms of Schizophrenia
		3.4 Conclusions and Recommendations for Translating Preclinical Findings to the Clinic
	4 Therapeutic Targeting of the DYN/KOR System in Major Depressive Disorder
		4.1 Preclinical Evidence for KOR Antidepressant Activity
		4.2 KOR Antagonists Show Efficacy in the FST Anti-depressant Screening Test
		4.3 Other Preclinical Models of Depression and Anxiety
		4.4 Nonselective KOR Antagonists as Antidepressants: Evidence from Buprenorphine and ALKS-5461
		4.5 KOR Antagonists Treatment of Anhedonia
		4.6 KOR Antagonists as Monotherapy vs Adjunctive Therapy
		4.7 Sex Differences
		4.8 Conclusions and Recommendations for Translation
	References
Imaging Kappa Opioid Receptors in the Living Brain with Positron Emission Tomography
	1 Introduction
		1.1 Neuroimaging with PET
		1.2 Concepts
	2 KOR-Targeting Radiotracers for Brain PET
		2.1 KOR Agonist PET Radiotracers
			2.1.1 Discovery and Preclinical Evaluation of [11C]GR103545
			2.1.2 [11C]GR103545 First-in-Human Evaluation
		2.2 2nd Generation KOR Agonist Radiotracers: [11C]EKAP and [11C]FEKAP
			2.2.1 Discovery and Preclinical Evaluation
			2.2.2 [11C]EKAP and [11C]FEKAP First-in-Human Evaluation
		2.3 KOR Antagonist Radiotracers
			2.3.1 Discovery and Preclinical Evaluation of [11C]LY2795050
			2.3.2 Discovery and Preclinical Evaluation of - [11C]/[18F]LY2459989
			2.3.3 First-in-Human Evaluation [11C]LY2795050 and [11C], [18F]LY2459989
	3 Small Animal Neuroimaging of KORs with PET
		3.1 Evaluation of KOR Radiotracers and PET Analysis in Rodents
		3.2 Application of KOR PET to Study Negative Affect in Rat
	4 Human KOR PET
		4.1 Alcohol Use Disorder (AUD)
		4.2 Cocaine Use Disorder (CUD)
		4.3 Social Stress
		4.4 Depression
		4.5 Sex Differences
		4.6 Drug Occupancy
	5 Conclusions
	References




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