What is the role of the H1 (histamine 1) receptor?

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From the Guidelines

The H1 (histamine 1) receptor plays a crucial role in mediating allergic responses, particularly in the context of anaphylaxis and allergic rhinitis.

Key Functions of H1 Receptors

  • Mediate allergic responses, including symptoms such as pruritus, flushing, and urticaria 1
  • Involved in the pathophysiology of anaphylaxis, with H1 receptors being the most clinically relevant 1
  • Play a key role in nasal obstruction in allergic rhinitis, inducing symptoms such as sneezing, nasal discharge, and nasal obstruction 1

H1 Receptor Antagonists

  • First-generation H1 antihistamines, such as diphenhydramine, hydroxyzine, and chlorpheniramine, are effective in treating allergic symptoms but have limitations due to sedation and anticholinergic effects 1
  • Second-generation H1 antihistamines, such as fexofenadine, loratadine, and desloratadine, are preferred due to their longer duration of action, less sedation, and fewer anticholinergic effects 1

Clinical Implications

  • H1 receptor antagonists are often used as adjunctive therapy for anaphylaxis, but should not be administered before or in place of epinephrine 1
  • In allergic rhinitis, H1 receptor antagonists can be used as monotherapy or in combination with other agents, such as intranasal corticosteroids, to manage symptoms 1

From the Research

Role of the H1 Receptor

The H1 receptor is a type of histamine receptor that plays a crucial role in various physiological and pathophysiological conditions. Some of the key functions of the H1 receptor include:

  • Mediating the central effects of histamine on alertness and wakefulness 2
  • Regulating the expression of pruritic factors, such as nerve growth factor and semaphorin 3A, in skin keratinocytes via histamine H1 receptor (H1R) 3
  • Inducing pro-inflammatory effects on T cells, B cells, monocytes, and lymphocytes 4
  • Mediating the bronchoconstrictive effects of histamine and increasing vascular permeability in the lung 4

Therapeutic Applications

The H1 receptor is a target for various therapeutic applications, including:

  • Treatment of allergy and insomnia with H1 receptor antagonists 2, 5
  • Relief of symptoms of allergic rhinitis with H1-receptor antagonists 4
  • Potential treatment of atopic dermatitis with next-generation antihistaminic agents possessing H1R and H4R antagonistic actions 3

Mechanism of Action

The mechanism of action of the H1 receptor involves:

  • Binding of histamine to the H1 receptor, which triggers a response 5
  • Inverse regulation of the H1 receptor by antihistamines, which utilize a shared phenyl group to block the movement of the toggle switch residue W4286.48 5
  • Potential introduction of new derivative groups to generate newer antihistamines through a secondary ligand-binding site in H1R 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study.

Allergology international : official journal of the Japanese Society of Allergology, 2014

Research

H1-receptors: localization and role in airway physiology and in immune functions.

The Journal of allergy and clinical immunology, 2003

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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