This book offers a comprehensive overview of the most important neurochemicals and approaches everything from the neurochemical’s perspective. It attempts to integrate the biochemical pathways of synthesis and metabolism of these neurochemicals with the disease states and point out the avenues of diagnostic testing and therapeutic intervention. Each chapter focuses on a specific neurochemical and provides a brief history, the biochemical profile, metabolism, physiological functions, and the clinical aspects. The clinical part of each chapter includes a discussion on disease states with either increased or reduced activity of the neurochemical and either activation or inhibition of the relevant receptors. This book is targeted toward practitioners and students of neuroscience and is written to emphasize the importance of these neurochemicals in the brain. With this emphasis on background neurochemical processes, the readers will be pointed towards logical diagnostic studies, laboratory investigations, and therapies based on the neurochemical dysfunction that underlies various disease states.
Author(s): Pradeep C. Bollu
Publisher: Springer
Year: 2022
Language: English
Pages: 319
City: Cham
Preface
Acknowledgments
Contents
Contributors
Chapter 1: Dopamine
Introduction
Physiology and Functions
Metabolism: Synthesis and Degradation
Dopamine Receptors
Dopaminergic Pathways
Dopamine, Parkinsonism, and DAT Scan
Dopamine and Psychiatric Disease
Tardive Dyskinesia
Dopamine and Punding
Dopamine and Restless Leg Syndrome
Dopamine, Sleep, and Wakefulness
Dopamine and Hypothalamus
Drugs Associated with Dopamine
Dopamine Precursor
Levodopa
Dopamine Agonists
Vesicular Monoamine Transporter (VMAT) Depletors
References
Chapter 2: Serotonin
History of Serotonin
Neurochemical Profile
Serotonin in the Brain
Serotonin in the Periphery
Raphe Nuclear System
Serotonin Receptors
Serotonin Metabolism
Chemical Structure and Biosynthesis
Serotonin Metabolism
Medications Acting on Serotonin System
Other Clinical Aspects
Serotonin in Migraine
Serotonin Effects on Heart
Serotonin in Psychosis
Serotonin Modulation in Obesity (Lorcaserin)
Serotonin in Nausea/Vomiting
Serotonin in Gut Motility
Serotonin Syndrome
Serotonin in RLS
References
Chapter 3: Adenosine
Introduction
Metabolism
Receptors
Alzheimer’s Disease and Autism
Sleep and Restless Leg Syndrome
Psychiatric Conditions
Epilepsy
Ischemia
Parkinson’s Disease
Huntington’s Disease
Multiple Sclerosis
Adenosine Agonists
Adenosine Antagonist: Caffeine
References
Chapter 4: GABA
History of GABA
Neurochemical Profile of GABA
GABA in Sleep
GABA in Neuronal Inhibition
GABA Receptors
GABAA Receptor
GABAB Receptor
GABA Metabolism
Medications Acting on the GABAergic System
Benzodiazepines
Barbiturates
Sodium Oxybate
Baclofen
Other Clinical Aspects
Antibody-Mediated Attack on GABA
GABA Antagonism and Improvement in Alertness: Role of Flumazenil in Hypersomnia
GABA in Restless Leg Syndrome (RLS)
References
Chapter 5: Glutamate
History
Neurochemical Profile
Glutamate and Neural Plasticity
Glutamate in Neurotoxicity
Receptors
Ionotropic Glutamate Receptors
NMDA Receptors
Non-NMDA Receptors
Metabotropic Glutamate Receptors
Metabolism
Glutamate Transporters
The Glutamate–Glutamine Cycle
GABA
Medications
Ketamine
Memantine
Riluzole
Topiramate
Felbamate
Pregabalin
Lamotrigine
Perampanel
Clinical Aspects
Role of Glutamate in Epilepsy
Role of Glutamate in Autoimmune Encephalitis
Role of Glutamate in Stroke
Role of Glutamate as a Dietary Toxin
Role of Glutamate in Neurodegeneration
References
Chapter 6: Glycine
Introduction
History
Receptors
The Glycine Receptor
The N-Methyl-D-Aspartic Acid Glutamate Receptor
The Glycine Transporters Type 1 and 2 Receptors
Neurochemical Profile
Neurotransmitter
Potentiating Action at the NMDA Receptors
The Role of Glycine Transporters
Metabolism
Synthesis
Uptake
Degradation
Pharmacology
Drugs Acting on Glycine Receptors
Strychnine
Ivermectin
Ethanol
Cannabinoids
General Anesthetics
Glutamate
Neuroactive Steroids
Tropeines
Zinc
Gelsemine
Other Allosteric Modulators
Drugs Acting on Glycine Reuptake
Bitopertin
Sarcosine
Other Selective Inhibitors
Clinical Aspects
Hyperekplexia
Glycine Encephalopathy
Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM)
Temporal Lobe Epilepsy
Psychiatric Disorders
Conclusion
References
Chapter 7: Histamine
History of Histamine
Neurochemical Profile
Tuberomammillary Nucleus and Histamine Pathways
Histamine in the Periphery
Histamine in Gastrointestinal System
Histamine in Immune System
Histamine Receptors
H1 Receptor
H2 Receptor
H3 Receptor
H4 Receptor
Ionotropic Receptors
Histamine Metabolism
Medications Acting via Histaminergic System
H1 Receptor Antagonists
H2 Receptor Antagonists
H3 Receptor Antagonists
H4 Receptor Antagonists
Other Clinical Aspects
Histamine in Alzheimer’s Disease
Histamine in Cognitive Disorders
References
Chapter 8: Melatonin
History of Melatonin
Neurochemical Profile
Melatonin and Sleep
Melatonin Receptors
Melatonin Metabolism
Medications Acting Via Melatonin System
Melatonin in Sleep
Melatonin in Depressive Disorders
Melatonin in Other Disorders
Other Clinical Aspects
Melatonin in Critical Care
Melatonin in Headaches
References
Chapter 9: Norepinephrine
Introduction
History of Norepinephrine
Neurochemical Profile
Norepinephrine Receptors
Norepinephrine Metabolism
Medications Acting on the Norepinephrine System
Selective Drugs
Alpha-1 Receptor Drugs
Alpha-2 Receptor Drugs
Beta-1 Receptor Drugs
Beta-2 Receptor Drugs
Beta-3 Receptor Drugs
Indirect Acting Agonists
Nonselective Drugs
Other Clinical Aspects
Alzheimer’s Disease
Parkinson’s Disease
Attention Deficit Hyperactivity Disorder (ADHD)
Schizophrenia
Depression
References
Chapter 10: Orexins
History of Orexins
Neurochemical Profile of Orexins
Orexin Receptors
Distribution of Orexin Receptors in the Brain
Orexin Receptor Signaling Mechanisms
Orexin Metabolism
Medications Acting Via Orexin System
Orexin Antagonist
Orexin 1 Receptor-Selective Antagonist
Orexin 2 Receptor-Selective Antagonist
Dual Orexin Receptor Antagonist (DORA)
Orexin Agonist
Other Clinical Aspects
References
Chapter 11: Acetylcholine
History
Neurochemical Profile
Central and Peripheral Nervous System Distribution of Ach
Acetylcholine in Sleep–Wake Cycle/Brenner’s Experiments
Ach in REM Sleep Generation
Acetylcholine in Memory Systems
Acetylcholine Receptors
Muscarinic Receptors
Nicotinic Receptors
Acetylcholine Metabolism
Synthesis
Storage
Hydrolysis
Choline Reuptake
Medications Acting on Acetylcholine System
Cholinomimetics/Parasympathomimetics [112]
Synthesis and Release Inhibitors [112]
Anticholinergics/Parasympatholytics
Other Clinical Aspects
Antibodies to Ach Receptors in Myasthenia Gravis
Dementia and Treatment with Cholinesterase Inhibitors
Pyridostigmine in Autonomic Dysfunction
Paroxysmal Nocturnal Dystonia/ADFE
Nicotine and Varenicline [112]
References
Chapter 12: Endorphins
Introduction
Metabolism: Synthesis and Degradation in the Body
Mechanism of Action
Physiological Effects
Clinical Aspects
Pain
Exercise
Mood and Psychiatric Disorders
References
Chapter 13: Neuropeptides and CGRP
History of Neuropeptides
Neurochemical Profile
Calcitonin Gene-Related Peptide (CGRP)
CGRP Structure, Receptors, and Metabolism
Medications Acting Via the CGRP Pathway
Other Clinical Aspects
References
Chapter 14: Galanin, Substance P, and Melanin-Concentrating Hormone
Galanin
Substance P
Melanin-Concentrating Hormone
References
Chapter 15: Neuroreceptors
Overview
G-Protein Coupled-Receptors (GPCRs)
GPCR Classification
Gα-GTP Amplification
Downstream Coupling of Gβγ
Termination of Signaling
Specificity of GPCR Signaling
Class A (Rhodopsin family) GPCRs
Class B (Secretin Family) GPCRs
Class C (Glutamate Receptor-Like) GPCRs
Class F (Frizzled/Taste Family) GPCRs
Adhesion Family GPCRs
Orphan G Protein-Coupled Receptors (oGPCRs)
Ligand-Gated Ion Channels
Ligand-Gated Ion Channel Classification
Ligand-Gated Ion Channel Structure
Ligand-Gated Ion Channel Signaling
Ligand-Gated Gamma Aminobutyric Acid (GABA)A Receptors
Ligand-Gated Glycine Receptors (GlyRs)
Ligand-Gated Nicotinic Acetylcholine Receptors (nAcRs)
Ligand-Gated 5-Hydroxytryptamine Type-3 (5-HT3) Receptors
Ligand-Gated Zinc-Activated Channel (ZAC) Receptors
Ligand-Gated Glutamate Receptors (GluRs)
Ligand-Gated Inositol 1,4,5-Trisphosphate (IP3) Receptors (IP3Rs)
Ligand-Gated P2X Receptors
Ligand-Gated Acid-Sensing (Proton-Gated) Ion Channel (ASIC) Receptors
Ligand-Gated Epithelial Sodium Channel (ENaC) Receptors
Enzyme-Linked Receptors
Receptor Tyrosine Kinases (RTKs) and Tyrosine-Kinase Associated Receptors (TKARs)
Receptor Serine–Threonine Kinase (RSTK)
Receptor Guanylate Cyclase (rGC)
Receptor Tyrosine Phosphatase (RTP)
Nuclear Receptors (NRs)
Nuclear Receptor Superfamily Classification
Nuclear Receptor–Ligand Interactions
Nuclear Receptor–DNA Signaling
Clinical Summary
References
Chapter 16: Pharmacokinetics and Pharmacodynamics
Overview
Absorption
Distribution
Metabolism
Elimination
References
Index
