Histamine

Histamine is a compound involved in local immune responses, regulates the gut, and acts as a neurotransmitter. Histamine is released by mast cells and excess histamine is involved in many of the symptoms of mast cell activation disorder.

Histamine dihydrochloride is an immunostimulant drug sold under the brand name Ceplene for acute myeloid leukemia.

Types of histamine receptors
All known histamine receptors are G-coupled.

H1 receptor
Location:
 * neurons
 * smooth muscle cells of the airways
 * blood vessels
 * widespread throughout the body

H2 receptor
Location: mostly in
 * gastric mucosa parietal cells
 * smooth muscle cells
 * heart

H3 receptor
Location:
 * mostly in histaminergic neurons, which moderate histamine, dopamine,serotonin, noradrenaline, and acetylcholine release in the central nervous system

H4 receptor
Location:
 * bone marrow
 * peripheral hematopoietic cells

Role of histamine in the body
Histamine stimulates inflammation by increasing blood flow to a site of infection or the region surrounding allergens, so your immune can engulf the foreign particle. It does this by causing the release of nitric oxide, which in turn causes vasodilation.

Modulating histamine levels
Histamine is broken down by an enzyme called diamine oxidase (DAO), which is found mainly in the gastrointestinal tract and in pregnant women, the placenta. Nutritional deficiencies in Vitamin C, magnesium, Vitamin B6 and copper – all DAO cofactors – can decrease DAO activity.

Vitamin C reduces blood histamine levels, potentially through several mechanisms: by inhibiting mast cell production; by increasing diamine oxidase (an enzyme that breaks down histamine); by inhibiting mast cell degranulation (and the release of histamine in the first place), and by inhibiting histidine decarboxylase (the enzyme that forms histamine).

Manganese and zinc can also prevent the release of histamine from mast cells.

Histamine intolerance
Histamine sensitivity can be a sign of mast cell activation disorder. Histamine Intolerance (HI) is a separate diagnosis.

Antihistamines
Antihistamines, also known as histamine antagonists help block the effects of histamine in the body. Classic antihistamines block H1 histamine receptors only.

Antihistamines include:

H1 receptor antihistamines

 * Cinnarizine - sedating
 * Diphenhydramine (some Benadryl products) - sedating
 * Hydroxyzine (Atarax/Vistaril) - sedating
 * Ketotifen - (Zaditor or Zaditen) - sedating, also a mast cell stabilizer
 * Promethazine (Phenergan) - Sedating
 * Triprolidine (Actifed) - sedating
 * Acrivastine (some Benadryl products)
 * Cetirizine (Zyrtec, some Benadryl products)
 * Chlorpheniramine maleate (Piriton)
 * Fexofenadine (Allegra)
 * Loratadine (Claritin)
 * Meclizine (antihistamine)
 * many others also exist

Uses of various H1 antagonists include:
 * allergies, sometimes including anaphylaxis
 * asthma
 * eczema
 * insomnia
 * itching including pruritus and urticaria
 * nausea and vomiting
 * vertigo
 * travel sickness
 * vertigo

H2 receptor antihistamines

 * Cimetidine (Tagament) - also blocks androgenic testosterone at high doses
 * Famotidine (Pepcid) - under investigation for Long COVID
 * Nizatidine (Axid)
 * Ranitidine (Zantac) - withdrawn from US market in 2020

H3 receptor antihistamines

 * Pitolisant (Wakix) which is licensed for narcolepsy
 * Betahistine (Serc) - typically used for vertigo and Ménière's disease (EU, UK, Australia) but not FDA approved
 * Ciproxifan and thioperamide - not in clinical use

H3R antagonists are being investigated for potential use in treatmenting of neurodegenerative diseases and sleep disorders, may reduce neuroinflammation and reduce cognitive dysfunction.

H4 receptor antihistamines
H4R antagonists are being investigated for use in allergies, and inflammatory conditions such as hayfever, chronic pruritus, and asthma.

Learn more

 * H1 Histamine Antagonists - DrugsBank Online
 * H2 Histamine Antagonists - DrugsBank Online
 * Biochemistry, Histamine - StatPearls
 * Rantidine - drugs.com