You’ve probably heard of antihistamines. They are popular over-the-counter drugs that people take to relieve allergy symptoms such as seasonal allergic rhinitis (hay fever), nasal congestion, sneezing, hives, among others. As their name suggests, antihistamines work by stopping a chemical called histamine from impacting the cells in your body.

What are Histamines?

Histamine is a chemical compound involved in the body’s immune responses. It also regulates physiological function in the gut and acts as a neurotransmitter, or a chemical messenger, for the brain. It is vital to the survival of many animals, including humans. Histamine is present in nearly all tissues of the body including the skin, intestines, brain, heart and lungs. It is stored in the mast cells as well as basophils, which are both types of white blood cells.

How do histamines work in the body?

Histamine plays a key role in the body’s allergic response. In response to a potentially harmful foreign body, histamines are released by our mast cells and bind to receptors on tissues.

There are four known receptors, designated H1-H4, which histamines can bind to, depending upon where they are released in the body, each resulting in different reactions.

  • H1 receptors are widely distributed in several tissues throughout the body, including the brain. It is commonly found in the smooth muscle from airways, cardiovascular system endothelial cells, and lymphocytes. Histamines binding to H1 receptors results in a series of responses in the body designed to remove foreign and potentially dangerous materials, including itchy skin, asthma, irregular heartbeats, and alterations in blood pressure2. Signals from histamines will make capillaries more permeable to white blood cells, which can attack these foreign bodies. Fluid is also able to move out of the capillaries more easily, leading to the allergy symptoms we recognise: runny nose, watering eyes3. Whilst these reactions are designed to protect the body from substances that may be harmful, in the case of allergies, these pathways are triggered, causing unpleasant and sometimes dangerous allergic reactions.
  • H1 receptors are found in the smooth muscles, vascular endothelial cells, gastrointestinal tract, urogenital tract, in the heart and the central nervous system. They are involved in the pathological process of allergy and occur in high density in areas involved in arousal and waking.
  • H2 receptors are found in the stomach lining and are involved in regulating the amount of gastric acid in the stomach. Histamine binding to H2 receptors causes the release of gastric acid.
  • H3 receptors are found throughout the nervous system and regulate histamine in the body by inhibiting further production of histamine.
  • H4 receptors regulate the release of white blood cells from the bone marrow. These receptors are located in the thymus, small intestine, spleen, colon, basophils and bone marrow.
Histamine Intolerance, Are You Suffering From Histamine Intolerance?


The Role of Antihistamines

Antihistamines are inexpensive, over-the-counter options for treating hay fever and allergies. They may be used as a temporary solution to manage allergies but will not resolve long-term chronic conditions like asthma, sinusitis, and mast cell activation syndrome. Although antihistamines are used to describe drugs for treating allergies, doctors use the term to describe a class of drug that opposes the activity of histamine receptors in the body. Antihistamines can be further classified according to the histamine receptor that they act upon, the two largest classes being H1-antihistamines and H2-antihistamines.

H1 Antihistamines

H1 Antihistamines bind to H1 receptors in the mast cells, smooth muscles, the endothelium in the body or the cells lining the inside of blood vessels and lymphatic vessels, and tuberomammillary nucleus in the brain located in the hypothalamus. H1-antihistamines are used to treat:

  • Allergic reactions in the nose (runny nose and sneezing)
  • Insomnia
  • Motion sickness
  • Vertigo caused by inner ear problems
  •  allergic reactions in the nose (e.g. runny nose and sneezing)

Common H1-antihistamines include:

  • Acrivastine
  • Cetirizine
  • Fexofenadine
  • Levocabastine
  • Azelastine (intranasal)
  • Desloratidine
  • Ebastine
  • Loratidine
  • Mizolastine
  • Tecastemizole  

H2 Antihistamines

H2 antihistamines bind to H2 receptors in the stomach and are used to treat conditions caused by excess stomach acid such as

  • Gastritis
  • Peptic ulcers
  • gastroesophageal reflux disease (GERD)
  • Zollinger-Ellison syndrome

Common H2 antihistamines include:

  • Ranitidine (Zantac)
  • Nizatidine (Axid)
  • Famotidine (Pepcid, Pepcid AC)
  • Cimetidine (Tagamet, Tagamet HB)

Learn more about the basics of histamine disorders, histamine buckets, and getting diagnosed with histamine intolerance or mast cell activation syndrome.