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.[1]
Types of histamine receptors[edit | edit source]
All known histamine receptors are G-coupled.[2]
H1 receptor[edit | edit source]
Location:
H2 receptor[edit | edit source]
Location: mostly in
- gastric mucosa parietal cells
- smooth muscle cells
- heart[2]
H3 receptor[edit | edit source]
Location:
- mostly in histaminergic neurons, which moderate histamine, dopamine,serotonin, noradrenaline, and acetylcholine release in the central nervous system[2]
H4 receptor[edit | edit source]
Location:
- bone marrow
- peripheral hematopoietic cells[2]
Role of histamine in the body[edit | edit source]
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.[citation needed]
Modulating histamine levels[edit | edit source]
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,[3][4][5] 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),[6] and by inhibiting histidine decarboxylase (the enzyme that forms histamine).[7]
Manganese and zinc can also prevent the release of histamine from mast cells.
Histamine intolerance[edit | edit source]
Histamine sensitivity can be a sign of mast cell activation disorder. Histamine Intolerance (HI) is a separate diagnosis.[8]
Antihistamines[edit | edit source]
Antihistamines, also known as histamine antagonists help block the effects of histamine in the body. Classic antihistamines block H1 histamine receptors only.[9]
Antihistamines include:
H1 receptor antihistamines[edit | edit source]
- 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[2][10][11]
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[10]
H2 receptor antihistamines[edit | edit source]
- 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[2][12][13]
H3 receptor antihistamines[edit | edit source]
- Pitolisant (Wakix) which is licensed for narcolepsy[14]
- Betahistine (Serc) - typically used for vertigo and Ménière's disease[15] (EU, UK, Australia) but not FDA approved
- Ciproxifan and thioperamide - not in clinical use[16]
H3R antagonists are being investigated for potential use in treatmenting of neurodegenerative diseases and sleep disorders, may reduce neuroinflammation and reduce cognitive dysfunction.[2][16]
H4 receptor antihistamines[edit | edit source]
H4R antagonists are being investigated for use in allergies, and inflammatory conditions such as hayfever, chronic pruritus, and asthma.[2]
See also[edit | edit source]
- Antihistamines (category)
- Diamine oxidase
- Low histamine diet
- Histamine N-methyltransferase
- Mast cell activation syndrome
- Mast cell activation disorder
Learn more[edit | edit source]
- H1 Histamine Antagonists - DrugsBank Online
- H2 Histamine Antagonists - DrugsBank Online
- Biochemistry, Histamine - StatPearls
- Rantidine - drugs.com
References[edit | edit source]
- ↑ "Histamine". PubChem. Retrieved January 6, 2022.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Patel, Raj H.; Mohiuddin, Shamim S. (2021). Biochemistry, Histamine. Treasure Island (FL): StatPearls Publishing. PMID 32491722.
- ↑ Clemetson, C.A. (April 1980), "Histamine and ascorbic acid in human blood", The Journal of Nutrition, 110 (4): 662–668, ISSN 0022-3166, PMID 7365537
- ↑ Johnston, C.S.; Martin, L.J.; Cai, X. (April 1992), "Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis", Journal of the American College of Nutrition, 11 (2): 172–176, ISSN 0731-5724, PMID 1578094
- ↑ Johnston, CS (December 1996). "Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults". J Am Coll Nutr.
- ↑ Mio, M (1999). "Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds". Immunopharmacology.
- ↑ Molderings, Gerhard (2016). "Pharmacological treatment options for mast cell activation disease". Naunyn Schmiedebergs Arch Pharmacol.
- ↑ "Histamine Intolerance: Symptoms, Diagnosis and The Food List". Histamine Intolerance. Retrieved January 6, 2022.
- ↑ "Histamine Antagonists". DrugBank Online. Retrieved February 18, 2021.
- ↑ 10.0 10.1 "Histamine H1 Antagonists". DrugBank Online. Retrieved January 6, 2022.
- ↑ "Classification of Antihistamines" (PDF). Medsafe - Government of New Zealand. Retrieved January 6, 2022.
- ↑ "H2 blockers". H2 blockers: MedlinePlus Medical Encyclopedia. Retrieved January 6, 2022.
- ↑ "Rantidine". drugs.com. Retrieved January 6, 2022.
- ↑ Harwell, Victoria; Fasinu, Pius (September 1, 2020). "Pitolisant and Other Histamine-3 Receptor Antagonists—An Update on Therapeutic Potentials and Clinical Prospects". Medicines. 7 (9): 55. doi:10.3390/medicines7090055. ISSN 2305-6320. PMC 7554886. PMID 32882898.
- ↑ Yuen, Melissa V.; Gianturco, Stephanie L.; Pavlech, Laura L.; Storm, KathenaD.; Yoon, SeJeong; Mattingly, Ashlee N. (December 2019). "Betahistine HCI: Summary Report" (PDF). University of Maryland Center of Excellence for Science and Innovation. Retrieved January 6, 2022.
- ↑ 16.0 16.1 Lin, Jian-Sheng; Sergeeva, Olga A.; Haas, Helmut L. (January 2011). "Histamine H3 receptors and sleep-wake regulation" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 336 (1): 17–23. doi:10.1124/jpet.110.170134. ISSN 1521-0103. PMID 20864502.
