Research in the field of histamine receptors over the past 100 years went hand-in-hand with the development of modern pharmacology. Advances in histamine research led by outstanding scientists was so incisive that the clinical approach to treat allergies and gastrointestinal ailments was revolutionized. The pharmacological treatment of peptic ulcer and gastroesophageal reflux was indeed a revolution, as it ended the surgical intervention. Interest in histamine pharmacology was resurrected by the discovery of another histamine receptor, number 4, using genomics-based reverse pharmacological approaches for screening orphan GPCRs. This receptor is preferentially expressed by immune cells and its discovery raised hopes for its translational exploitation as a new therapeutic target for unmet medical needs ranging from asthma to cancer. However, several drawbacks emerged and dramatically slowed down research in the field.A better understanding of receptor intra-and interspecies heterogeneity will certainly improve and accelerate the translation of experimental data into clinical practice. Also, the plethora of data on brain histamine is hinting at a fundamental role of this system as a hub that receives internal and peripheral stimuli to allocate the necessary excitation to specific brain circuits that preside the appropriate behavioral responses.
The development of new histaminergic ligands is an ongoing process that constantly provide new preclinical tools.The aim of this book is to cover the most important aspects of histamine receptor function and pharmacology in the central nervous system and to provide a comprehensive overview of the preclinical and clinical advances made in recent decades and the exciting prospects for the future. It highlights the clinical areas where there is a great need for new therapeutic approaches and where novel histaminergic agents may be useful for personalized medicine.
Author(s): Kazuhiko Yanai, Maria Beatrice Passani
Series: Current Topics in Behavioral Neurosciences, 59
Publisher: Springer
Year: 2022
Language: English
Pages: 462
City: Cham
Preface
Contents
Part I: Pharmacology and Medicinal Chemistry
New Chemical Biology Tools for the Histamine Receptor Family
1 Introduction
2 New Histamine Receptor Tools
2.1 Structural Biology of Histamine Receptors
2.2 Biosensors to Detect Conformational Changes of Histamine Receptors
3 New Histamine Receptor Ligands
3.1 Covalent Ligands for the Histamine Receptors
3.2 Fluorescent Ligands for the Histamine Receptors
3.3 Histamine Receptor Photopharmacology
4 Concluding Remarks
References
Chemical Probes for Histamine Receptor Subtypes
1 Introduction
1.1 Chemical Probes
1.2 Physiology of Histamine
1.2.1 Biosynthesis and Metabolism
1.2.2 Histamine Receptors
Histamine H1 Receptor
Histamine H2 Receptor
Histamine H3 Receptor
Histamine H4 Receptor
2 In Vitro Assays
2.1 Reference Ligands
2.1.1 Histamine H1 Receptor
Agonists
Antagonists
2.1.2 Histamine H2 Receptor
Agonists
Antagonists
2.1.3 Histamine H3-Receptor
Agonists
Antagonists
2.1.4 Histamine H4 Receptor
Agonists
Antagonists
Multi-target Histamine Ligands
2.2 Labelled Ligands
2.2.1 Radiolabelled Ligands
2.2.2 Fluorescent-Labelled Receptor Ligands
3 In Vivo Assays
3.1 Histamine H1 Receptor
3.1.1 Agonists
3.1.2 Antagonists
3.2 Histamine H2 Receptor
3.2.1 Agonists
3.2.2 Antagonists
3.2.3 COVID Effects
3.3 Histamine H3 Receptor
3.3.1 Agonists
3.3.2 Antagonists
3.4 Histamine H4 Receptor
3.4.1 Agonists
3.4.2 Antagonists
4 Conclusion
References
Patho-Pharmacological Research of Anti-allergic Natural Products Targeting Antihistamine-Sensitive and -Insensitive Allergic M...
1 Introduction
2 Up- and Down-Regulations of Histamine H1 Receptors as Rate-Limiting Mechanisms of Signal Transduction
3 H1R Gene as a Susceptibility Gene
3.1 Activation of H1R Gene Expression in Nasal Mucosa of Allergic Rhinitis Model Rats
3.2 Correlative Activation of IL-4, IL-5 and Histidine Decarboxylase (HDC) Gene Expression to H1R Gene Expression
3.3 Alleviation of Symptoms in TDI Rats by Sophorae radix (Kujin): An Anti-allergic Kampo Medicine
4 Antihistamine-Insensitive Mechanism of Allergy and Combination Therapy
4.1 Discovery of Antihistamine-Insensitive Mechanism of Allergy Using Suplatast Tosilate
4.2 Discovery and Molecular Pharmacology of Compounds Suppressing IL-9 Gene Expression from Natural Sources
5 Future Outlook for the Therapy of Allergic Diseases
5.1 Multiple Pathological Mechanisms of Allergic Diseases
5.2 A New Evaluation System to Develop New Therapeutics
5.3 Therapeutic Strategy for Multifactorial Allergic Diseases
6 Expanding Histamine Research for the Novel Therapeutic Strategy of H1R-Related Diseases in Future
6.1 H1R and Diabetes Mellitus and Other Diseases
6.2 H1R Signaling-Related Diseases in the Brain
6.3 Strategy of the Therapy for Diseases Susceptible to H1R Gene Expression
References
Molecular Signaling and Transcriptional Regulation of Histamine H1 Receptor Gene
1 Introduction
2 Signaling Pathway of H1R-Activated Gene Expression
3 Molecular Signaling of H1R Gene Expression
3.1 Molecular Signaling of H1R Gene Expression in HeLa Cells
3.1.1 HeLa Cells Endogenously Express H1R
3.2 Signaling Pathway of H1R-Mediated H1R Gene Expression Induced by Stimulation with Histamine in HeLa Cells
3.3 Identification of Heat Shock Protein 90 (Hsp90) Involved in the Signaling Pathway of H1R Gene Expression in HeLa Cells
3.4 Signaling Pathway of H1R-Mediated H1R Gene Expression Induced by Stimulation with Histamine in U373 Cells
3.5 Up-Regulation of H1R Gene by Signal Molecules Other than Histamine
4 Regulation of H1R Gene Transcription
4.1 Promoter Analysis of Human H1R Gene
4.2 Transcriptional Regulation of H1R Gene in HeLa Cells
4.3 Transcriptional Regulation of H1R Gene in U373 Cells
References
Part II: Clinical Pharmacology
Histamine Neuroimaging in Stress-Related Disorders
1 Introduction
2 Histaminergic Function in Depression
3 Histaminergic Function in Anorexia Nervosa
4 Histaminergic Function in Brain-Gut Interactions and Irritable Bowel Syndrome
5 Summary of the Data and Future Direction
6 Conclusion
References
Histamine-4 Receptor: Emerging Target for the Treatment of Neurological Diseases
1 Introduction
1.1 Neurobiology of Histamine
1.2 Neurobiology of the H4R
2 Neurological Diseases and H4R
2.1 Parkinson´s Disease (PD)
2.2 Amyotrophic Lateral Sclerosis (ALS)
3 Concluding Remarks and Future Perspectives
References
Imaging Histamine H3 Receptors with Positron Emission Tomography
1 H3 Receptor Quantification Using PET
1.1 Positron Emission Tomography
1.2 Radioligand Properties for PET Imaging
1.3 Principles of PET Signal Quantification
1.4 Use of PET to Study Occupancy of Receptors by Drugs in Humans
2 Presentation of H3 PET Studies According to Radioligands Used
2.1 [11C]GSK189254
2.1.1 Studies with [11C]GSK189254 and GSK189254
2.1.2 Studies with [11C]GSK189254 and PF-03654746
2.1.3 Studies with [11C]GSK189254 and GSK239512
2.1.4 Studies with [11C]GSK189254 and AZD5213
2.1.5 Studies with [11C]GSK189254 and Pitolisant
2.2 Studies with [11C]MK-8278
2.2.1 Studies with [11C]MK-8278 and MK-0249
2.2.2 Studies with [11C]MK-8278 and MK-3134
2.3 Studies with [11C]TASP457
2.3.1 PET Evaluation of [11C]TASP457
2.3.2 Evaluation of In Vivo Role of H3R with [11C]TASP457
2.4 Studies with [18F]FMH3
3 Discussion
4 Conclusion
References
Therapeutic Potential of Histamine H3 Receptors in Substance Use Disorders
1 Introduction
1.1 Alcohol
1.2 Nicotine
1.3 Psychostimulant
1.4 Clinical Translation of H3R Ligands for Substance Use Disorders
1.5 Conclusions
References
Efficacy and Safety of Non-brain Penetrating H1-Antihistamines for the Treatment of Allergic Diseases
1 Classification of Antihistamines
2 Constitutive Activity of Histamine H1 Receptors
3 Efficacy and Potency of AHs
4 Functions of the Histaminergic Nervous System in the Brain
5 Central Effects of Sedating AHs
6 Evaluation of the Sedating Effects via H1RO
7 Recent Topics in the Clinical Pharmacokinetics of AHs
7.1 In Vivo Brain RT of AHs in the Human Brain
7.2 Brain Penetrability of AH in Eye Drops
7.3 Transdermal Patch AH Preparation
8 AHs Present in OTC Rhinitis Drugs and OTC Common Cold Drugs
9 Cardiotoxicity of Sedating AHs
10 Conclusion and Perspectives
References
Part III: The Immune and Inflammatory Response in the Brain
The Histamine and Multiple Sclerosis Alliance: Pleiotropic Actions and Functional Validation
1 The Histamine System
2 From Central and Peripheral Inflammation to Myelination Defects in MS
3 An Overview of Histamine Preclinical Studies
3.1 Targeting H1 Receptor
3.2 Targeting H2 Receptor
3.3 Targeting H3 Receptor
3.4 Targeting H4 Receptor
3.5 Targeting HDC
3.6 Combinatorial Histamine Receptor Actions
4 Histamine Markers in Biological Fluids and CNS Tissues from MS Patients
5 Toward a Histamine-Based Pharmacology in MS Patients
6 Concluding Remarks
References
Histamine and Microglia
1 Microglia
2 Histamine
3 Histamine and In Vitro Microglial Functions
3.1 Histamine H1 Receptor
3.2 Histamine H2 Receptor
3.3 Histamine H3 Receptor
3.4 Histamine H4 Receptor
3.5 Histidine Decarboxylase
4 Histamine and In Vivo Microglial Functions
4.1 Amyotrophic Lateral Sclerosis
4.2 Parkinson´s Disease
4.3 Brain Ischemia
4.4 Depression-Like Behaviors
4.5 Interaction with Brain-Resident Mast Cells
5 Future Perspectives
References
Histamine in the Crosstalk Between Innate Immune Cells and Neurons: Relevance for Brain Homeostasis and Disease
1 Overview of the Functions of Histamine in the Brain
2 The Functions of Histamine in Innate Immune Cells
2.1 Microglia
2.2 Monocytes/Macrophages
3 The Role of Histamine in Neurodegenerative Diseases
3.1 Parkinson´s Disease
3.2 Stroke
4 Conclusions/Perspectives
References
Part IV: Neuropharmacology: Histamine and Behaviour
The Histamine System in Zebrafish Brain: Organization, Receptors, and Behavioral Roles
1 Zebrafish in Behavioral Neuroscience
2 Histamine in Fish
3 Histaminergic Systems in Fish
3.1 Fish in General
3.2 Zebrafish Brain Histamine System
4 Histamine Receptors in Zebrafish
5 Behavioral Roles of Histamine in Zebrafish
6 Plasticity of the Zebrafish Histamine System
References
Different Peas in the Same Pod: The Histaminergic Neuronal Heterogeneity
1 Introduction
2 Histamine in the Central Nervous System
3 Brain Functions Modulated by Histamine
4 Stress Reveals Diversities Among Histamine Neurons
5 Some Histamine Neurons Release GABA
6 Microdialysis Studies
7 Differential Genes Expression Distinguishes Functional Subpopulations of TMN Neurons
8 Histamine Neurons Display Electrophysiological Heterogeneity
9 Where Do We Go from Here? Testing the Functional Diversity of Histaminergic Pathways in Learning and Memory
References
Histamine: A Key Neuromodulator of Memory Consolidation and Retrieval
1 Overview
2 Histamine-Producing Neurons and Histamine Receptors in the Brain
3 Histamine and Memory Consolidation
4 Histamine and Memory Retrieval
5 Histamine and Other Memory Processes
6 Effects of the Genetic Manipulation of Histamine Signaling on Learning and Memory
7 Activity of Histamine Neurons In Vitro and In Vivo
8 Human Histaminergic System and Memory
9 Conclusions and Perspectives
References
Targeting Histamine and Histamine Receptors for the Precise Regulation of Feeding
1 Histamine in Feeding
1.1 Histamine in Satiety and Satiation
1.2 Histamine in Feeding Motivation
1.3 Histamine in Food Taste Perception and Memory
1.4 Histamine in Feeding Circadian Rhythm
2 Histamine Receptors in Feeding
2.1 Histamine H1 Receptor: A Putative Downstream Target
2.2 Histamine H2 Receptor: A Dispensable Receptor for Feeding?
2.3 Histamine H3 Receptor: A Unique Mechanism Involved?
2.4 Histamine H4 Receptor: A Receptor Awaiting Exploration
2.5 Clinical Trials of Chemicals Targeting Histaminergic Receptors
3 Functional Diversity of Histamine: What Shall We Do Next?
3.1 Diverse Functions of Histamine in Different Phases of Feeding
3.2 Circuit Basis for the Functional Switching of Histamine in Feeding
3.3 Precise Regulation of Feeding Behaviors Through Histamine Receptors
4 Conclusions
References
A Duet Between Histamine and Oleoylethanolamide in the Control of Homeostatic and Cognitive Processes
1 Introduction
2 Virtuoso Solo of Brain Histamine
3 Virtuoso Solo of Oleoylethanolamide
4 Histamine and OEA Partnership in Eating Behaviour
5 OEA Requires Histaminergic Neurotransmission to Promote Its Procognitive Effects
6 Histamine and OEA Partnership in Alleviating Stress and Depression
7 Histamine Controls Liver Ketogenesis Via Oleoylethanolamide Signalling
8 Conclusions
References
Part V: Neuropharmacology: Histamine and Sleep
Histamine as an Alert Signal in the Brain
1 Introduction
2 Sleep-Wake Behavior of Genetic Mouse Models
3 Narcolepsy and Histaminergic Neurons
4 Clock Gene Expression
5 Conclusions
References
Brain Mast Cells in Sleep and Behavioral Regulation
1 Introduction
2 Brain Mast Cells Are Pluripotent Cells That Have Multiple Interacting Chemical and Neural Systems
3 Brain Mast Cells and Sleep and Behavioral Regulations
4 Neuroimmune Involvement in Sleep and Psychiatric Diseases
5 Mast Cell Deficient Mice Exhibit Altered Sleep Changes at Baseline and After Sleep Deprivation
6 Arousal Response During Food Deprivation Was Blunted in Mast Cell Deficient Mice
7 A Histamine Release Enhancer, Compound 48/80, Enhances Wakefulness in WT Mice, But Not in Mast Cell Deficient Mice
8 Mast Cell Deficient Mice Showed Attenuated Responses to Sleep-Inducing Histamine H1 Antagonists
9 A New Inducible and Kit-Independent Mast Cell Deficient, Mas-TRECK (Toxin Receptor Knockout) Mouse
10 Brain-Resident Mast Cells and Neurobehaviors
11 Chronic Sleep Loss and Abnormal Glycometabolism and Mast Cell Involvements
12 Conclusions
References
The Role of the Central Histaminergic System in Behavioral State Control
1 The Anatomic Tuberomammillary Hypothalamus (TMN)
2 Histamine Synthesis, Storage, Release, Degradation, and Reuptake
3 Other TMN Neurotransmitters
4 Histamine Receptors
4.1 H1 Receptors
4.2 H2 Receptors
4.3 H3 Receptors
5 Cell Diversity Within the Histamine Cell Group
6 Afferent and Efferent Projections of the TMN Neurons
7 Histamine Levels During Sleep and Wake Cycle
8 Histamine in Behavioral State Control
9 Histamine Drugs for Treating Sleep Disorders
10 Conclusions
References
