Main description:

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.

Contents:

PHARMACOLOGY AND MEDICINAL CHEMISTRY. A novel fluorescent histamine H(1) receptor antagonist demonstrates the advantage of using fluorescence correlation spectroscopy to study the binding of lipophilic ligands.- Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs.- Covalent Inhibition of the Histamine H(3) Receptor.- A Photoswitchable Agonist for the Histamine H(3) Receptor, a Prototypic Family A G-Protein-Coupled Receptor.- Epigenetics meets GPCR: inhibition of histone H3 methyltransferase (G9a) and histamine H3 receptor for Prader-Willi Syndrome.- CLINICAL PHARMACOLOGY. Cardiac safety of second-generation H1 -antihistamines when updosed in chronic spontaneous urticaria.- Risk of first-generation H1-antihistamines: a GA(2)LEN position paper.- The Reliability of Histamine Pharmacodynamic Response Phenotype Classification in Children With Allergic Disease.- Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice.- Irritable bowel syndrome and histamine. Increased Brain Histamine H1 Receptor Binding in Patients with Anorexia Nervosa.- Interactions of the histamine and hypocretin systems in CNS disorders. THE IMMUNE AND INFLAMMATORY RESPONSE IN THE BRAIN. Histamine beyond its effects on allergy: Potential therapeutic benefits for the treatment of Amyotrophic Lateral Sclerosis (ALS).- JNJ10181457, a histamine H3 receptor inverse agonist, regulates in vivo microglial functions and improves depression-like behaviours in mice.- Histaminergic Neurons in the Tuberomammillary Nucleus as a Control Centre for Wakefulness.- Effect of Royal Jelly and Brazilian Green Propolis on the Signaling for Histamine H(1) Receptor and Interleukin-9 Gene Expressions Responsible for the Pathogenesis of the Allergic Rhinitis.- Elucidation of Inverse Agonist Activity of Bilastine.- Histamine modulates hippocampal inflammation and neurogenesis in adult mice. NEUROPHARMACOLOGY: HISTAMINE AND BEHAVIOUR. Embryonic exposure to valproic acid affects the histaminergic system and the social behaviour of adult zebrafish (Danio rerio).- Neuronal histamine and the memory of emotionally salient events.- Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories.- Histamine H1 Receptors in Neural Stem Cells Are Required for the Promotion of Neurogenesis Conferred by H3 Receptor Antagonism following Traumatic Brain Injury.- Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake. NEUROPHARMACOLOGY: HISTAMINE AND SLEEP. Genetic lesioning of histamine neurons increases sleep-wake fragmentation and reveals their contribution to modafinil-induced wakefulness.- Histamine: neural circuits and new medications.- Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.- Optogenetic-mediated release of histamine reveals distal and autoregulatory mechanisms for controlling arousal.- Impaired histaminergic neurotransmission in children with narcolepsy type 1.