eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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2/2019
vol. 15
 
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abstract:
Commentary

New antihistamines – perspectives in the treatment of some allergic and inflammatory disorders

Jan Tatarkiewicz
,
Przemysław Rzodkiewicz
,
Małgorzata Żochowska
,
Anna Staniszewska
,
Magdalena Bujalska-Zadrożny

Arch Med Sci 2019; 15, 2: 537–553
Online publish date: 2019/02/04
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Introduction

Histamine [H] is a well-known biogenic amine whose biological properties were first characterized more than 100 years ago [1, 2]. It plays a significant role in the human organism as a mediator and neurotransmitter. Histamine is produced in many types of tissues including immune cells, gastric mucosa, central nervous system (CNS), smooth muscles, sensory nerves, heart, etc. Histamine-producing cells may be divided into two types: professional and non-professional [3]. Professional histamine-producing cells such as mast cells, basophils, enterochromaffin-like cells of the gastric mucosa, and histaminergic neurons synthesize this mediator, collect it in special granules inside the cells and release it in large amounts after specific stimulation. In non-professional histamine-producing cells, histamine is synthesized and crosses the cell membrane with specific carrier proteins according to the concentration gradient. The non-professional histamine-producing cells include many other cell types, among them dendritic cells (DCs) [4] and T cells [5].
Histamine is involved in numerous physiological and pathophysiological processes [6] – immunological response, immunomodulation, inflammation, allergic response, gastric acid secretion, cell proliferation, wound healing, cognitive function, memory, sleep cycle, endocrine homeostasis – and has an influence on release of other neurotransmitters [7] and modulation of tumor growth [8].
Histamine exerts its effect through four types of G-protein coupled receptors: H1, H2, H3, and H4 [6, 7, 9, 10]. Histamine interacts with its receptors with different affinities. The most susceptible are histamine H3 and H4 receptors (H3Rs and H4Rs, respectively), whereas the activation of H1 and H2 receptors (H1Rs and H2Rs, respectively) requires significantly higher concentrations of histamine [11]. It is suggested that in some disorders in which classic antihistamines (i.e. drugs antagonizing histamine effects at H1 receptors) were not effective, it might be possible to control them using novel histamine receptor ligands acting at H3 and/or H4 receptors [6, 12].

Methods of review

The authors searched the electronic database MEDLINE (PubMed, https://www.ncbi.nlm.nih.gov/pubmed/; until January 15th, 2017) using the following population search terms: H3 OR H4 combined using the Boolean operator AND with the term receptor*. These search results were focused by combination using the...


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