Histamine pharmacology: four years on

Abstract

The histamine field has moved on rapidly in the last four years, with expansion in roles and clinical development, particularly in the newest two of four histamine receptors. This themed volume is a testament to this expansion with 16 original and review articles spanning a wide spectrum of histamine-related topics, with therapeutic translational relevance to addiction, dementias, anxiety disorders, cancers, vestibular disorders, migraine and autoimmune disorders. LINKED ARTICLESThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 Abbreviations EHRS, European Histamine Research Society; ESF COST, European Science Foundation Cooperation in Science and TechnologyHistamine [(2-(imidazol-4-yl) ethylamine] is a biogenic amine that has been a favourite among pharmacologists since the inception of the discipline in the early 20th century with the classic experiments of Sir Henry Dale. It can be considered as the 'pleiotropy' master amine with key roles in cell immune defence, nutrition, neurological activity, growth, development and fertility. This themed volume is a follow-up of a highly successful volume in 2009, which was published at the beginning of European Science Foundation Cooperation in Science and Technology (ESF COST) Action BM0806 focused on histamine, particularly histamine H4R research. This year represents the completion of this highly successful 4 year Action, which was praised by the European Union as a prime example of best practice. This volume is dedicated to the memory of two premier histaminologists who contributed profoundly to the basic and clinical pharmacology of histamine, namely Professors Sir James Black and Walter Schunack, particularly related to the pharmacology of H2 and H3 receptors respectively. Many members of the COST Action and the European Histamine Research Society (EHRS), including myself, have been profoundly influenced by both men, and have contributed pieces published in this present themed volume in honour of their memory. This is an exciting period as both H3 and H4 receptor-directed compounds have entered advanced clinical development, both targets offering promising new therapies for many largely poorly treated central and peripheral pathologies respectively. The reviews cover a range of topical areas relating to histamine and its role in neutrophils, the latest examples of mast cell stabilizers, central histamine receptors, particularly H3R and drug addiction, crosstalk between histamine and its aminergic cousins and finally an exciting new integrated structural chemogenomic method to define molecular and structural motifs for ligand binding and selectivity for histamine receptors, which has significant implications for the whole GPCR superfamily.Intra-and intercellular crosstalk among histamine and amine-related components has important pathophysiological consequences, as reviewed in detail by Sánchez-Jiménez et al. (2013). Histamine and the immune system ...

Granulocytes in Ocular HSV-1 Infection: Opposing Roles of Mast Cells and Neutrophils

“…Kit W-sh mice have lower basal levels of histamine than WT mice, 40 and may respond to histamine differently. The pharmacologic impact of histamine is a complex and often controversial topic due to variable expression patterns of its four receptors, H 1 R-H 4 R. 41,42 Neutrophils are the most abundant leukocyte population that extravasates into the cornea upon HSV-1 infection.…”

Procognitive impact of ciproxifan (a histaminergic H3 receptor antagonist) on contextual memory retrieval after acute stress

“…The histamine H 3 receptor is a central inhibitory autoreceptor located on histaminergic nerve terminals that are found mainly on cholinergic and dopaminergic neurons. H3 receptor activation resulted in a reduction of the release of histamine in the brain, whereas its inhibition (by inverse agonist or antagonist) increased the release of histamine. Ciproxifan (cyclopropyl 4‐(3‐(1H‐imidazol‐4‐yl)propyloxy) phenyl ketone) is an extremely potent histamine H 3 receptor (H 3 R) inverse agonist/antagonist which enhanced the release of histamine and increases sustained attention and alertness states .…”

Histamine Intolerance Originates in the Gut

“…Generally, histamine was discovered more than 100 years ago. The understanding of the central role of histamine in allergies and in immune regulations has led to the development of antihistamine medications [ 8 ].…”